# EPA Registration Jacket 2517

‐133

# EXponent

June 15,2010

Richard Gebken Product Manager 10 Document Processing Desk Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
Subject: Response to EPA Notice ofRegistration

Dear Mr. Gebken: Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 200)6
telephone 202-772-4900 facsimile 202-772-4979 www.exponent.com



### On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158 th 

### Plaza, Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a response to EPA's Notice ofRegistration (dated April 30, 20 I0) for the following product:

• EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies (EPA File Symbol 2517- 133).

The purpose ofthis letter is to address the requirement 13. a) Data to fulfill the OPPTS Guideline 830.1800

-- Enforcement Analytical Method submitted within 45 days ofthe approvals. This study has been submitted under separate cover and an MRID has not yet been assigned.

Ifyou have any questions, please contact me at 202-772-4932.


### sifiCeJi ly Y7 

# (**/--~j** ,
s B. Messina orized Representative of VSergeant's Pet Care Products, Inc.

Enclosures

cc: Kevin Sweeney, EPA Kelly Hoskins, Sergeant's ;, );



# . );' ,Please read instructions on reverse before completing form Form Approved OMS No 2070-0060 Approval expires 05-31-98 

# EPA United States Environmental Protection Agency Washington. DC 20460 D_Registration DAmendment 

# C2J Other OPP Identifier Number

Application for Pesticide

- Section I
1. Company/Product Number 2517-133 4. Company/Product (Name) Sergeant's Pet Care Products, Inc./ EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies 2. EPA Product Manager Richard Gebken
PM#10 3. Proposed Classification

!:8JNone DRestricted

5. Name and Address of Applicant (Include ZIP Code) Sergeant's Pet Care Products, Inc. 6. Expedited Review. In accordance with FIFRA Section 3(c)(3)(b)(I). my product is similar or identical in composition and labeling to:
2625 South 1581h Plaza Omaha, NE 68130 

## D Check ifthis is a new address 

# o Amendment

- Explain below.

!:8J Resubmission in response to Agency letter dated 4/30/2010 

# o Notification

- Explain below. EPA Reg. No.

Product Name

Section" 

# o Final printed labels in response to Agency letter dated XX-XX-XX 

# o "Me Too" Application 

# o Other

- Explain below. Explanation: Use additional page(s) if necessary. (For section I and Section II.) Response to EPA providing Enforcement Analytical Method.

1. Material This Product Will Be Packaged In: Child-Resistant Packaging DYes" ONo

'Certification must be submitted Unit Packaging DYes 

# o No If "Yes" No. per Unit Packaging wgt. Container Section '"

Water Soluble Packaging DYes 

# o No It "Yes" Package wgt. 

## I No. per Container

3. Location of Net Contents Information 4. Size(s) Retail Container DLabel D Container

6. Manner in Which Label is Affixed to Product DLithOgraph DPaper glued DStenciled DOther

Section IV 2. Type of Container 

# o Metal DplaStic
DGlass DPaper OOther (Specify) Plastic Bag
5. Location of Label Directions DOn Can DOn Labeling accompanying product

1. Contact Point (Complete items directly below for identification ofindividual to be contacted, ifnecessary, to process this application.)
Name Title Telephone No. (Include Area Code) James Messina .

Authorized Representative 202-772-4932**~------------------------------------------L-------------------~----------------~---------,c~~~~----------~** Certification
, J J ) ) .' ) /).)**ba~** Application I certify that the statements I have made on this form and all attachments thereto are true, accurate and complet,e. I**~ ~eceived**  acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both [Stamped) under app.uCable law/I )}-**~** ) J.**~** ; J.) i) 2. Signatt e 

# Vi

3. Title ' BY' /....... Authorized Representative J J ) ) J

.**I·'j/~** ;**I------H---I'---------+:~::___::_:__._::_=------"'-** 

### --I 4. Typed Name:

# /J
James Messina 5. Date: June 15, 2010 :, ;) 

### ,

.) J"

,), , 

### , ,Sergeant's Pet Care Products, Inc.

2625 South 158th Plaza • Omaha, NE 68130-1770 • Telephone 402.938.7000 • Fax 402.938.7099 • www.sergeants.com

October 28, 2010

Front Processing Desk Richard Gebken PM 10 U.s. Environmental Protection Agency Office ofpesticide Program (7505 P) Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501

SUBJECT: Gold Seal Certificates

Dear Mr. Gebken,
Following is a list ofproducts that Sergeant's would like to receive six Gold Seal Certificates for each product. I have enclosed two printed labels for each ofthe products listed.

EPA No. 2517-129 Cyphenothrin+Pyriproxyfen Squeeze-On for Dogs (20%) Product labels: Sergeant's EVOLVE 21 Flea & Tick Squeeze-On for Dogs Sergeant's EVOLVE 40 Flea & Tick Squeeze-On for Dogs SENTRYPRO XFT 21 flea & tick squeeze-on for dogs SENTRYPRO XFT 40 flea & tick squeeze-on for dogs

EPA No. 2517-130 Product labels: Cyphenothrin+Pyriproxyfen Squeeze-On for Dogs (30%)
Sergeant's EVOLVE 61 Flea & Tick Squeeze-On for Dogs SENTRYPRO XFT 61 flea & tick squeeze-on for dogs

EPA No. 2517-133 EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies Product labels: Sergeant's EVOLVE II Flea & Tick Squeeze-On for Dogs SENTRYPRO XFT II flea & tick squeeze-on for dogs SENTRYPRO TOY & small breed flea & tick squeeze-on for dogs (4 to 10 Ibs) Sergeant's TOY BREED Flea & Tick Squeeze-On for Small Breed Dogs (4 to 10 Ibs.)

Should you need further information, I can be reached at (402)938-7065 or my e-mail address is skane@sergeants.com.

Thank you for your assistance in this matter.

Susan Kane Regulatory Specialist Sergeant's Pet Care Products, Inc.UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES

November 26, 2010
I, Richard Gebken, Insecticide Branch, Registration Division, Office of Pesticide Programs, Office of Prevention, Pesticides and Toxic Substances, United States Environmental Protection Agency ("EPA"), certify that the pesticide product (s) listed below is, as of the date of this letter, a registered product under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended, and that as such, the product(s) may be sold and marketed in the United States of America as authorized and limited by FIFRA. A true and correct copy ofthe product label approved by EPA is attached to accompany this letter.
Registration of this product(s) with EPA also denotes that the registrant listed below is responsible for ensuring full compliance with all the laws of the United States of America, or governing jurisdiction, regarding the sale, storage and/or disposal of the product(s). Further, the recipient of this letter is on notice that the referenced registration and/or the accompanying label may change subsequent to the date of this letter. EPA assumes no responsibility to notify the recipient(s) ofthis letter of any change in the status of theregistration(s) and/or the product label for the product(s) listed below.

EPA has issued registration numbers for the product(s) listed below to:
Sergeant's Pet Care Products, Inc. 2625 South 158Th Plaza Omaha, NE 681301703

EPA Registration Number: 2517-133 Name of Product: ETOFENPROXINYLAR SPOT-ON FLEA AND TICK FOR**DO~** & PUPPIES

# ~:.~.~**Jl'R'i~ken** Risk Manager 13 Insecticide Branch Registration Division (7505P)

# Material to be added to an e-Jacket/Jacket
Reg. No. 2517-133
Description: New Label

1. Placement within the e-Jacket/jacket: X Default: (chronological, top 

## = newest)
D 

## File Location: (PDF page number, i.e., "before page 

## 45")

2. X Send to Data Extraction contractors this material: X Newly stamped accepted label

D 

## Notification X New CSF (3/6/10 

## are CSFs of record) X Other: 

# Correspondence

3. Attach this coversheet to the top of the material orjacket. It must be well organized and clipped together, NOT STAPLED. Then give the material with this coversheet to staff in the Information Services Center (Room S-4900).


# Reviewer's Name: Kevin Sweeney

Phone: ----.:3::....:0::....:5:::.....-...=;5-=0-=6=3

____ Division: -.:R:....:..D=-

__ Date: 05/03/2010

Created May 3, 2010U.S. ENVIRONMENTAL PROTECTION AGENCY Office ofPesticide Programs Registration Division (7505P) 1200 Pennsylvania Ave., N.W.

Washington, D.C. 20460

NOTICE OF PESTICIDE:



## o Registration 

### o Reregistration
(under the Federal Insecticide, Fungicide, and Rodenticide Act, as amended)

Name and Address ofRegistrant (include ZIP Code): Sergeant's Pet Care Products, Inc. 2625 South 158'h Plaza Omaha, NE 68130 EPA Registration No. Date ofIssuance:


### 2517-133 

### APR 30 2010

Term ofIssuance:
Conditional Registration Expires April 

### 30, 2012
Name ofPesticide Product: EtofenproxlNylar Spot-on Flea and

Tick for Dogs and Puppies

On the basis ofinformation furnished by the registrant, the above named pesticide is hereby registered under the Federal Insecticide, Fungicide and Rodenticide Act.
Registration is in no way to be construed as an endorsement or recommendation ofthis product by the Agency. In order to protect health and the environment, the Administrator, on his motion, may at any time suspend or cancel the registration ofa pesticide in accordance with the Act. The acceptance ofany name in connection with tbe registration ofa product under this Act is not to be construed as giving the registrant a right to exclusive use ofthe
name or to its use if it has been covered by others.

This product is conditionally registered in accordance witb FIFRA sec. 3(c)(7)(a) provided that:

1. This registration is time-limited and expires two years from the date this product is first released for shipment.

You must provide the Agency with a projected release for shipment date within 30 days ofthe date ofthis Notice ofRegistration. The Agency will calculate the expiration date based on the projected release for shipment date until an actual release for shipment date is provided in writing.

2. Only one confidential statement offormula (basic) will be filed for this product; no alternate formulation or minor formulation statements may be submitted or approved for this product.

3. Make the following changes to the label:

a. All marketing statements and references to "mosquitoes" throughout the draft label must be deleted because the submitted efficacy study do not support these claims. West Nile virus and heartworm claims must also be removed

b. On page one ofthe label, because all "mosquito" references are not permitted, you must correct the marketing statements that refer to "[Five] [5] Way Protection" to "[Four] [4] Way Protection

. .. "c. The claim "New [fonnulaJ" may appear on product produced for 6 months from the date of first distribution only.

d. Revise the EPA Registration Number to read: "EPA Registration No. 2517-133.

e. Remove the phrase "Before they can

... " made with reference to transmission ofdisease by ticks. There are no data to support this claim.

f. Ofthe three statements proposed, you may use: "Some dogs may experience temporary startle effects when this product is applied." in the Precautionary Statements section ofthe label.

g. Change the second weight class for dogs from 10-201bs to 11-20Ibs.

4. All ofthe product chemistry data requirements for this product have been satisfied, except for OPPTS Guidelines 830.6317 and 830.6320, Storage Stability and Corrosion Characteristics studies, respectively. Within on-year ofthe date ofthis registration you must submit these data including interim reports made at 0, 3, 6, 9, and 12 month intervals.

5. You must submit enhanced incident reports for this product on a quarterly basis beginning July I, 2010. Please flag any Confidential Business Infonnation as such. Enhanced incident reporting should be submitted to the Product Manager. Quarterly sales information should be submitted to the Registration Division, Immediate Office (ATTN: Kimberly Nesci).

The following is a list ofinfonnation needed by EPA to better characterize these incidents:

EPA Registration Number Product name (brand name) Lot # Where purchased: internet, store, veterinarian Active Ingredient(s) Weight range for product

Date on which incident occurred. (mmldd/yyyy) State in which the incident occurred. (standard 2 letter abbreviation) Registrant case #
Species: dog, cat, other (specifY) Breed: (as reported by pet owner) Age: months or years Sex: M, F, or neutered Weight: pounds
Primary Route ofExposure: dennal, oral, other animal, inhalation, other Body System: neurological, dermatological, GI, respiratory, ocular, other Major signs noted with separate column for each sign, using standard terminology Time to Onset: (hours, days) Treated by veterinarian: yes or no First time product used: yes or no Misuse: use on incorrect species, overdose, too frequent dosing, other (describe) Any known precondition EPA Severity Code: death, major, moderate, minorOutcome: died, recovered, still treated, unknown

6. Along with the enhanced incident reporting, you must submit an analysis ofthe incidents seen, to include the following details:

All incidents should be reported including all minor dermal and ocular irritation reports.
Summary table for dogs showing number ofincidents ofeach severity code for each route ofexposure. Each incident should only be reported once. Ifone incident has several routes ofexposure, the order should be ocular> oral> dermal. In other words, an incident with both oral and dermal exposure would be reported as oral exposure, and an incident with both ocular and oral exposure would be reported as ocular exposure.

A similar summary table for cats (misuse or secondary exposure) showing number of incidents ofeach severity code for each route ofexposure.
Summary table for dogs and table for cats showing number ofincidents that are believed due to secondary exposure (e.g., multi-pet households).

A summary table for dogs showing number ofincidents for each severity code for these age ranges: <3 months, 3-6 months, 6-9 months, 9-12 months, I yr, 2 yr, 3 yr, 4 yr, 5 yr, 6 yr, 7yr,8yr,9yr, 10yr, II yr, 12yr, I3yr, 14yr, 15 yr, >15 yr.

A summary table showing the number ofdog incidents for each severity code for each pet weight range on the product label.

A summary table for dog weight showing number ofincidents for each product weight range. This table should show number ofincidents in dogs weighing less than that product weight range, number ofincidents in dogs in lower halfofweight range, number of incidents in dogs in upper halfofweight range, and dogs weighing more than the product weight range.

Table showing number ofincidents for each dog breed.

Table showing number ofincidents in dogs for each clinical sign.

Table showing number ofincidents in dogs for each organ system.
Report aggregate incidents, but do not combine moderate and minor incidents.

7. You must submit and/or cite all data required for registration ofyour product under FIFRA Section 3(c)(5) when the Agency requires all registrants ofsimilar products to submit such data, and submit acceptable responses required for reregistration ofyour product under FIFRA section 4.

8. The basic Confidential Statement ofFormula dated April 28, 2010 is acceptable, and is the basic CSF ofrecord, superseding all previously submitted CSFs. As stated above, only one confidential statement offormula (basic) will be filed for this product; no alternate formulation or minor formulation statements may be submitted or approved for this product.9. The acute toxicity profile for this product is as follows:

Route ofExposure

Acute oral toxicity Acute dermal toxicity Acute inhalation toxicity Primary eye irritation Primary skin irritation Dermal sensitization Toxicity Category

IV IV IV III IV Negative

A stamped copy ofthe label and copies ofthe Data Evaluation Records (DERs) are included for your file. Two copies ofthe finished labeling must be submitted prior to releasing the product for shipment. Ifthese conditions are not complied with, the registration will be subject to cancellation in accordance with FIFRA sec. 6(e). Your release for shipment ofthe product constitutes acceptance ofthese conditions.

IfEPA determines that future mitigation measures are necessary for all pet spot-ons, the Agency will inform registrants. Ifmitigation measures are necessary, EPA may take regulatory action. Ifyou have any questions concerning this registration, please contact Kevin Sweeney at (703) 305-5063.

Si".,ra,hm'. Date: 

### APR 3 0 2010

EPA Fonn 8570-6

Enclosure

# Sergeant's Pet Care Products, Inc. Master Label
29 April 2010 EPA Reg. No. 2517-RGG Infonnation in I I is optional. Page I of4 EPA SAL FRONT PANEL DOG SQUEEZE

- ON Pyriproxyfen (NYLAR), Etofenprox Editors Note: [Optional proposed text appears in hmckcls -the final Jabd mu} blCh,de some or all ofthe optional text!
ETOFENPROXJNYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES
{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On} {ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small breed dogs} {ABN: Sergeant's Toy Breed Flea and Tick Squceze-On for small and toy breed dogs] {ABN: Sergeant's Small Breed Flea and Tick Squeeze-On} fABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small breed dogs) {ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for dogs} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for Dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small breed dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small and toy breed dogs) {ABN: Sergeant's® Evolve (4) Flea and Tick Squeeze-On for Dogs (and Puppies)} {ABN: Sergeant's® Evolve (10) Flea and Tick Squeeze-On for Dogs (and Puppies)} {ABN: SentryPro® XFTC (4) Flea and Tick Squeeze-On for Dogs (and Puppies)} {ABN: SentryPro® XFTC (10) Flea and Tick Squeeze-On for Dogs (and Puppies)}
[One Application:(choose from the following)]

• [with nylar®]

• [(One) (Two) (Three) (Four) (XX) Applications]

• [Bonus] 33% more [now includes 4 tubes]

• [odorless] [unscented] [fragrance free]

• [Dries quickly] [Quick drying formula] [Quick Drying]

• [Squeeze-On] [stays on and doesn't rub oftl

• [Spreads by using the dog's natural skin oils]

• [Breaks the flea life cycle for up to (70 Days) (9 Weeks)]

• [Controls reinfestation for up to (70 days) (9 weeks)]

• [For toy breeds 4-10 Ibs.]

• [For small breeds 10·20 Ibs.]

• [For toy and small breeds [4-10][ 10-20]lbs.]

• [Specially formulated for small breed[s] dogs]

• [Specially formulated for toy breed[s] [dogs]]

• [Specially formulated for [toy breed[s]] and [small breed[s]] dogs]

• [Toy] [and] [small] breed formula]

• [Gentle protection for [toy] [small] breed dogs]

• [5 Way Protection]

• [Controls fleas, ticks, flea eggs & larvae] ACCEP'l"El) with 

### COMMENTS

# in~p~If~'~ Under the Fedem1 Insecticide, Fungtclde, and Rodenticide Act. as amended. for' the pesticfde regtst6D "",der EPA Reg. No, 

### ''S17 -13 

### 3

• [Kills Fleas, Ticks, Flea Eggs. Larvae] [and] [repels mosquitoes [for up to one month] [for up to 4 weeks]]

• [Flea, tick, flea egg and larvae control]

• [Kills fleas and ticks for up to [30 days] [4 weeks]]

• [Kills ticks [for up to [30 days] [4 weeks]]]

• [Kills Ticks] [Before they can] [that] [transmit Lyme Disease

• [Kills [adult] fleas for up to [30 days) [4 weeks]]

• [Kills Fleas and Ticks] [for up to [30 days][4 weeks]]

• [Flea, Tick and Flea Egg Protection]

• [Repels mosquitoes [for up to one month] [for up to 4 weeks]]

• [Flea and Tick control]

• [Kills fleas that may cause flea allergy dermatitis. and flea bite anemia] [for up to [30 days] [4 weeks)]

• [Kills Flea Eggs and Larvae for up to (9 weeks) (70 days) (per application)]

# Sergeant's Pet Care Products, Inc. Master Label

29 April 2010 EPA Reg. No. 2517-RGG Information in I I is optional. Page 2 of4 EPA SAL

• [Prevents flea eggs from developing mto biting adults for up to (9 weeks) (70 days) (per application)]

• [Repels mosquitoes that may transmit [heartworm] [West Nile virus] [from feeding on dogs] [for up to [one month] [30 daysll4 weeks]]

• [Repels Mosquitoes] [Prevents mosquitoes that transmit West Nile virus and heartworm] [from feeding on dogs] [for up to [one month] [30 daysl[ 4 weeks])
FRONT PANEL

ACTIVE INGREDIENTS: DOG SQUEEZE

- ON Pyriproxyfen (NYLAR), Etofenprox

Etofenprox

.................................................................................... 55.00% Pyriproxyfen

.................................................................................. 2.20% OTHER INGREDIENTS:

....................................................................... 42.80% TOTAL 100.00%
[Nylar' is a registered trademark of MCLaughlin Gormley King Company

### 1

KEEP OUT OF REACH OF CHILDREN 

### CAUTION See IBackllorllSidel Label Panells} for Additional Precautionary Statements

NET CONTENTS: IOnellTwoliThreeliFourllFiveliSixl2.0 mL applicators. [for small dogs 4 to 10IbsJ IOnellTwoliThreellFourllFiveliSixl4.0 mL applicators. [for small dogs 10 to 20 IbsJ

# Sergeant's Pet Care Products, Inc. Master Label

29 April 2010 EPA Reg. No. 2517-RGG Infonnation in I 

### I is optional. Page 3 of4 EPA SAL BACK PANEL DOG SQUEEZE

- ON Pyriproxyfen (NYLAR), Etofenprox 

## {Product Name}
READ ENTIRE LABEL BEFORE EACH USE

PRECAUTIONARY STATEMENTS HAZARDS TO HUMANS AND DOMESTIC ANIMALS CAUTION

HAZARDS TO HUMANS: Causes moderate eye irritation. Avoid contact with eyes and clothing. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum. or using tobacco.

HAZARDS TO DOMESTIC ANIMALS: For External Use Only. Do not use on dogs under 13 weeks of age. Consult a veterinarian before using this product on debilitated. aged, medicated. pr'egnant. or nursing animals. Sensitivities may occur after using ANY pesticide product for pets. Ifsigns of sensitivity occur, bathe your pet with mild soap and rinse with large amounts ofwater. Ifsigns continue. consult a veterinarian immediately.
{Some dogs may startle when a room temperature squeeze-on is applied.][Some dogs may experience temporary startle effects when a squeeze-on is applied.J{Some dogs may experience temporary startle etTects when squcezeon's are applied.]

FIRST AID
IF IN EY ES: Hold eye open and rinse slowly and gently with water for 15-20 minutes. Remove contact lenses, if present, after the first 5 minutes. and then continue rinsing. Call a poison control center or doctor for treatment advice. Have the product container or label with you when calling a poison control Center or doctor or going for treatment. You may also contact 1-800-781-4738 for emergency medical treatment infomlation.

PHYSICAL OR CHEMICAL HAZARDS: Combustible: Do not use or store near heat or open flame.

DIRECTIONS FOR USE It is a violation of Federal Law to use this product in a manner inconsistent with its labeling.

Do not get this product in your pet's eyes or mouth. Do not apply more often than {once a month] {once every 30 days]. Use only on Dogs. FOR EXTERNAL USE ON DOGS ONLY. Do not use on puppies less than 13 weeks ofage. Weigh your dog to be sure you are applying the right dose formulated for the weight ofyour pel. Do not treat your pet with more than one pesticide product at a time. Over dosing your animal can result in serious illness and even death. Best if used year round. Do not bathe pet with in the first 24 hours after squeeze-on has been applied. Households with more than one pet should not allow dogs or cats to groom each other until solution has dried. DO NOT USE ON CATS or animals other than dogs. Separate the treated dog from all other dogs and cats for 24 hours after treatment has been applied. Cats or dogs that actively groom or engage in close physical contact with treated dogs may be at risk ofserious harmful effects. Ifyour dog is exhibiting signs of and/or are being treated for skin dermatitis, talk to your vet before applying any topical flea and tick control product. Sensitivtties may occur after using ANY pesticide product on pets, It is recommended to separate treated dogs from other household pets for 24 hours after treatment has been applied, If signs of sensitivity occur, bathe your dog with mild soap and rinse with large amounts ofwater.

FOR USE ON DOGS: Weighing 4 TO 10 LBS.

- Apply contents ofone (2.0 mL) tube [vial] of IProduct NameliSqueeze-on I as a spot high on the back ofthe dog's neck behind its head and apply as a stripe to a point midway between the neck and the tail. (INSERT DIAGRAM THAT DEPICTS APPLICATION OF PRODUCT ON THE DOG)

FOR USE ON DOGS: Weighing 10 TO 20LBS.

- Apply contents ofone (4.0 mL) tube [vial] of )product NameliSqueeze-on 

### I as a spot high on the back ofthe dog's neck behind its head and apply as a stripe to a point midway between the neck and the tail.

# Sergeant's Pet Care Products, Inc. Master Label

29 Aprii2010 EPA Reg. No. 2517-RGG Information in 

### I I is optional. Page 4 of4 EPA SAL (INSERT DIAGRAM THAT DEPICTS APPLICATION OF PRODUCT ON THE DOG)

HOW TO APPLY: Remove product tube [vial} from the package. Holding tube [viall with notched end pointing up and away from the face and body cut or tear offthe narrow end at the notches. While holding the animal with one hand. use the other hand to apply the solution. Invert the tube b'iatj and use the narrow end to part the animal's hair while gently squeezing to app!y to the animal's skin. Hold the animal for a few seconds to give the solution time to be absorbed into the animal's coat. When finished. wrap the tube [vial] in paper and put into the trash.

# Sergeant's Pet Care Products, Inc. Master Label

29 April 20 I 0 Infonnation in 

### I I is optional. 

### BACK PANEL Page 5 of

. 

### t; EPA Reg. No. 25 I7-RGG EPA SAL 

### DOG SQUEEZE

- ON Pyriproxyfen (NYLAR), Etofenprox

STORAGE AND DISPOSAL Do not contaminate water, food or feed by storage or disposal. PESTICIDE STORAGE: Do not remove tube ITom the pack until ready to use. Store in a cool (below 25 GC) dry place out ofreach ofchildren. Do not re frigerate. Protect from direct sunlight.

PESTICIDE DISPOSAL: Nonrefillable container. Do not reuse or refill this container. Offer for recycling or reconditioning, ifavailable and appropriate. Ifempty: Do not reuse this container. Place in trash or offer for recycling ifavailable. If partly filled: Call your local solid waste agency tor disposal instructions. Never place unused product down any indoor or outdoor drain.

[WARRANTY Read the entire Directions for Use and Warranty before using this Product. By using this product, user or buyer accepts the following warranty. [[The directions for use ofthis product are believed to be adequate and must be follo\

...'cd carefully. However, it is impossible to eliminate all risks inherently associated with the use ofthis product. Unintended consequences may resu It because of such factors as weather conditions, presence or absence ofother materials, or the manner ofapplication, all ofwhich are beyond the control ofScrgeanfs Pet Care Products, fnc

.. ]) Sergeant's Pet Care Products, Jnc. is committed to providing high quality products. To the extent consistent with applicable law, Sergeant's Pet Care Products. Inc. makes no warranties. express or implied. ofmerchantability or of fitness for a particular purpose or otherwise, that extend beyond statements on this label. To the extent consistent with applicable law. Sergeant's Pet Care Products, Inc

.. the manufacturer, or the Seller disclaims any liability whatsoever for special. incidental, or consequential damages resulting from the use ofthis product. To the extent consistent with the law, the exclusive remedy ofthe user or buyer shall not exceed the purchase price paid.)
[Sergeant's Care Pet Products, Inc. is committed to providing high quality products. If you have questions or comments about this product. please write: Sergeant's Consumer Response. P.O. Box 5403Q9. Omaha. NE 68154- 0399.1

In Case of Emergency, call: 1-800-781-4738 Non-Emergency call: 1-800-224-PETS (7387)

Distributed by:
Sergeant's Pet Care Products, Inc. PO Box 540224 Omaha. NE 68154 {END

- BACK I SIDE PANEL}

TUBE / VIAL LABEL 

### Front Label {product Name} Etofenprox

..........55.0% W/W Pyriproxyfen

.........2.2% W IW [For more information] [Visit us at]**~\\\'\\.**..**5'<;_I:g<';_~llJ_ts:com** Made in USA

EPA Reg. No. 2517-XX EPA Est. No. XXXXXXX {date & label code}

Back Label

KEEP OUT OF REACH OF CHILDREN 

### I CA UTION: Read directions and precautions before using. [2.0][4.0j mL {label code} EPA REG. No. 2517-XX lIabel code} 

# IROUTING AND TRANSMITTAL SLIP Date April 30, 2010

TO: (Name, office symbol, room number, building, Agency/Post) 

## Vi'"' 

# ;.t!3o'bo70 1. Marion Johnson (7505P) "-

# fJ

. 2. I 

# I
3.

xxx Action xxx File Note and Return
xxx For Concurrence For Clearance Per Conversation
xxx As ReQuested For Correction Prepare Reoly Circulate xxx For Your Information See Me Comment Investigate Signature Coordination Justify REMARKS



### 2517-133 Registration for EtofenproxlNylar Spot-on for Dogs and Puppies

DO NOT use this form as a RECORD of approvals, concurrences, disposals, clearances, and similar actions. FROM: (Name, org. symbol, Agency/Post)
Kevin 

### J. Sweeney Room No.- Bldg. 8-7238 Potomac Yard

Phone No. (703) 305-5063

### DOSE ADMINISTERED TO DOGS TREATED WITH**ETOFENPRO~YLARPRODUCT** 

### Dose required for efficacious application to fleas and ticks = 250mglkg



### Product a.i. content: 55% etofenprox 2.2% pyriproxyfen
Etofenprox is the only a.i. oftoxicological concern for humans and domestic animals.



### Product Density is 1.035g1ml, equivalent to 0.56925g etofenproxlml



### Conversions used 1 kg = 

### 2.205 lbs. 1 kg 

## = 1000g 1 g = 1000mg Dog (lbs) / 2.2051bs = 

### kg


### Etofenprox (mg) = 0.56925g1ml x #ml x 1000mg/kg


### Etofenprox Dose = 

### etofenprox (mg)/(kg) dog


### Highest Dose in Companion Animal Study 758 mglkg according to study. I calculated 766 mg/kg based on density reported in recent product chemistry data. Consultant says 689.7mglkg. EPA reviews do not express dose in mg/kg as a regulatory endpoint. Review states that 2.0 ml dose for 4-20 lbs weight class is acceptable.

In original application the registrant proposed 4-20 lbs. dog weight class. Efficacy data from registrant clearly show that the minimum dose required for efficacy against fleas and ticks is 250 mglkg. Registrant revised label on April 29 and proposed two weight classes: 4-10 lbs. and 11-20Ibs.

### Weight Class I 

### = 4-10 Ibs.

Labeled Dog Dog Product Etofenprox Weight (Ibs.) Mass (kg) Dose (ml) Etofenprox (mg) Dose (mg/kg)

4 1.81 2.0 1138.50 629.00 5 2.27 2.0 1138.50 501.54 6 2.72 2.0 1138.50 418.57 7 3.17 2.0 1138.50 359.15 8 3.63 2.0 1138.50 313.64 9 4.08 2.0 1138.50 279.04 10 4.54 2.0 1138.50 250.77


### Weight Class II 

### = 11-20 Ibs

Labeled Dog Dog Product Etofenprox Weight (Ibs.) Mass (kg) Dose (ml) Etofenprox (mg) Dose (mg/kg)

11 4.99 4.0 2277.00 456.31 12 5.44 4.0 2277.00 418.57 13 5.90 4.0 2277.00 385.93 14 6.35 4.0 2277.00 358.58 15 6.80 4.0 2277.00 334.85 16 7.26 4.0 2277.00 313.64 17 7.71 4.0 2277.00 295.33 18 8.16 4.0 2277.00 279.04 19 8.62 4.0 2277.00 264.15 20 9.07 4.0 2277.00 251.04

### April 29, 2010 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION



### MEMORANDUM


### Subject: Name ofPesticide Product: ETOFENPROXINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES EPA Reg. No. IFile 

### Symbol: 2517-RGG DP Barcode: DP 376746 Decision No.: 420097 Action Code: R310 PC Codes:

From: 128965 (Etofenprox: 55%) 129032 (Pyriproxyfen: 2.2%) 

# r-:---0**~** Byron T. Backus, Ph.D., Toxicologist 

# n**~** I , l 

### = Technical Review Branch 

# <f**~** 

### "L. 

## i - L"'" 

# O .

. A.,. \ 

### Registration Division (7505P) 

# i**U-~--~** 

### To: Kevin SweeneylRichard Gebken, RM 13 Insecticide Branch Registration Division (7505P)
Registrant: SERGEANT'S PET CARE PRODUCTS, INC.

FORMULATION FROM LABEL:

Active IngredientCs): 128965 Etofenprox 129032 Pyriproxyfen Other IngredientCs): TOTAL

ACTION REQUESTED: 

### The Risk Manager requests:

"TOX: Review response to companion animal safety review."

Page I of7 

### Bywt. 55.00%

2.20% 42.80% 100.00%

### BACKGROUND:



### The material received includes responses to comments in a previous TRB review (February 24, 20 I0) ofa companion animal safety study (MRID 47849609). In addition, there is a label (dated 10 September 2009) which indicates a dosage rate of2.0 mL for small dogs weighing from 4 to 201bs.

COMMENTS AND RECOMMENDATIONS:



### I. We can accept the registrant's arguments regarding the numbers ofdogs (combining Groups A2 and B3) treated at a 5X dosage rate with Substance II (55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31 % pyriproxyfen).

2. While we would have preferred to have two separate studies (one with puppies, the other with adult dogs), the current 870.7200 Companion Animal Safety Guidelines state: "The age of animals in the study is dependant upon label claims. Ifonly adults (6 months or older) are the targeted population ofanimals to receive treatment, adults only will suffice. However, ifa product is registered for use on pediatric animals (i.e. puppies

...), the label should state a minimum age for this group, for example, "Do not use on puppies

.. .less than eight weeks of age". Consequently, the product should be tested in 8 week-old animals in the companion animal safety study." There is the additional stipulation: "At least six animals per sex should be used at each dosage level."

3. From the original study report, Group Al puppies weighed from 4.66 to 12.23 lb (2.12 to 5.56 kg) and were dosed once with from 3.1 to 7.5 mL [or from 1.5 to 3.75X the dosage rate of2.0 mLl Substance II, while Group A2 puppies weighed from 5.94 to 16.11b (2.7 to 7.32 kg) and

were dosed with cumulative amounts of 18.8 to 50 mL [or from 9.4 to 25X the dosage rate of2.0 mLl Substance II. One Group B3 adult weighed 8.95 lbs (4.06 kg) and was treated with a cumulative amount of 12.5 mL (5 x 2.5 mL, or 7.5X the dosage rate of2,0 mL), while the remaining B3 dogs weighed from 15.4 to 20.llb (7.0 to 9.1 kg) and were each treated with a cumulative amount of22.5 mL (5 x 4.5 mL, or 11.25X the dosage rate of2.0 mL) Substance II.

4. The registrant has presented statistics (Table 4) evaluating the % change body weight/day for the different puppy groups. These statistics show no significant differences between Groups AI, A2, and their controls (Cl) with respect to this parameter for the periods from day 1 to 7,7-14, and for 1-14.

5. The registrant has presented statistics (Table 3) evaluating the % change body weight/day for Group B3 and C2 (a control group) adult dogs. These statistics show a significant difference (P < 

### 0.05) between these groups (with Group B3 showing reduced gains) with respect to this parameter for the periods from day I to 7 and from day I to 14 (but no significance for the period from day 7-14). This has to be considered an effect ofexposure. From the original study report (see p. 36 ofMRID 47849609) it is noted that individual daily food consumption was not reported in grams but by a scoring system (Fc 1 = 

### 0-25%, Fc 2 >25-50%, Fc 3 >50-75%, and Fc 4> 75-100%), and it is considered unlikely by this reviewer that the resulting data would be robust enough to show whether or not a moderate drop in food consumption actually occurred in the B3 (or any) group from day I to 7.
Page 2 of7

### 6. The material from the registrant includes (Table 5) a listing ofthe ages ofthe puppies. Group A2 ranged from 73 to 106 days (mean: 87.2), with only two puppies 84 days (12 weeks) ofage
or less. Group Al ranged from 79 to 99 days (mean: 91.5), with only one puppy 84 days (12 weeks) ofage or less. Group CI ranged from 91-106 days ofage. It 

### is recommended that the proposed label treatment age be raised from 12 to 13 weeks (or to 3 months).

7. The registrant has provided a comment (letter dated II March 2010) from the investigator regarding the behavioral effect (response?) in some puppies immediately following topical application. According to this letter: "Two of six puppies in Al and four of six in group A2 did

some running in circles immediately after application. It 

### lasted one or two circles in the pen and then they calmed down. No scratching or attempts at licking. No vocalization... Our impression was that the puppies were stimulated by the application ofa liquid. They got used to the effect ofbeing wet and no similar signs were seen after the following applications

..." However, the response also includes the following: "The question that needs is answering is "why only the test item groups"?

.. A subjective conclusion was that the test items may have been cold (or felt cold, maybe as a result ofevaporation?). That could be the reason why the pups did not react after the next applications and also why no signs were seen on the skin and why no other changes were recorded

..."

Since this effect was not seen in controls, it has to be considered an effect ofthe test substance. As there were no indications of scratching or licking at the application site, no vocalization, and the puppies calmed down within a short period oftime, it can be considered a minor effect. However, it is recommended that there be a statement on the label noting this effect can occur but that the dog should quickly calm down.

8. The revised executive summary (incorporating the above comments) is attached. The study is upgraded to Acceptable.

9. TRB concludes that the companion animal safety study in MRID 47849609 will support the proposed dosage rate of2.0 mL (ofthe formulation containing 55% Etofenprox and 2.2% Pyriproxyfen) on 4-20 lb dogs with retreatment at monthly (30-day) intervals.

Page 3 of7EPA Reviewer: Byron T. Backns, Ph.D. Technical Review Branch, Registration Division (7505P)

EPA Secondary Reviewer: Ayaad Assad, DVM, Ph.D. Toxicology and Epidemiology Branch, HED (7509P) Signature: 

# Or**~** 

# n-t-,

Date: 0 ""

- 

## 'L-l

- 1.. 0 \ 0 Signature: 

# An**{£~ ~**  Date:

# ~a?ilJ:~ I DATA EVALUATION RECORD 

# I

Note: This document contains only a revised Executive Summary

STUDY TYPE: Companion animal safety study- dogs/puppies

- OPPTS 870.7200

PC CODE: 128965- Ethofenprox, 129032- Pyriproxyfen, DP BARCODE: 371676

TEST MATERIAL (PURITy): Cyphenothrin (8.2% w/w), Fipronil (9.8% m/w), Etofenprox (55.16% w/w), S-Methoprene (8.78% w/w), Methoprene (8.90% w/w) and Pyriproxifen (2.31 % and 2.43% w/w)

TRADE NAME: Not provided

CITATION: De1port, P.C. (2009) Companion animal safety evaluation on dogs of spot-on products containing multiple toxicants and insect growth regulators. Clin Vet International (Pty) Ltd., Bloemfontein, Republic of South Africa. Study No. CV 08/551, August 6, 2009. MRID 47849609. Unpublished.

Miller, T. (2010) Response to February 24th, 2010, Decision 420097, 2517-RGG, Re: Etofenprox/Nylar Spot-On Flea & Tick for Dogs and Puppies.

SPONSOR: Sergeant's Pet Care Products, Plano, Texas

REVISED EXECUTIVE SUMMARY: In a companion animal safety study (MRID 47849609), groups ofrandom-source adult (> 6 months ofage) andjuvenile (10-15 weeks of age) dogs were topically administered 3 combinations ofinsecticides and insect growth regulators or one inert substance. Two groups ofthree male and three femalejuvenile dogs were administered test substance IA (8.2% w/w cyphenothrin and 9.8% m/w fipronil; Batch No. 012003-09) and test substance II (55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w pyriproxifen; Batch No. 011901-09) at either IX (recommended dose) or 5X (recommended dose hourly for 5 applications). The test substances were applied simultaneously as adjacent stripes along the dorswn ofthe dog from behind the ears caudally to the base ofthe tail. Two groups ofthree male and three female adult dogs weighing 9-20 kg were administered the test substance IA and test substance III (8.90% w/w methoprene and 2.43% w/w pyriproxifen; Batch No. 011902-09) at either IX (recommended dose) or 5X (recommended dose hourly for 5

Page 40f7

### applications). The test substances were applied as previously described. A group ofthree male and three female adult dogs weighing less than 9 kg was administered test substance II at 5X (recommended dose hourly for 5 applications). A group ofthree male and three female juvenile dogs and another group ofthree male and three female adult dogs were administered control substance IVA (Batch No. 012004-09) containing inert ingredients (not otherwise stated) at 5X the recommended dose. The groups and test materials they received are shown in the table below:

Group

A Group Al (n-6) Puppies (10-15 weeks) Group A2 (n-6) Puppies (10-15 weeks) Single application ofsubstance IA Five applications ofsubstance IA Single application ofsubstance II Five applications ofsubstance II

B Group Bl (n-6) Adults (9-20 kg) Group B2 (n-6) Adults (9-20 kg) Single application ofsubstance IA Five applications ofsubstance IA Single application ofsubstance III Five applications ofsubstance III C Group CI (n-6) Puppies (10-15 weekS) Group C2 (n-6) Adults (9-20 kg) Five applications control substance IVA Five applications control ofsubstance IVA Substance IA containS 8.2% w/w cyphenothnn and 9.8% m/w fipronrL Substance II contains 55.16% **w/w** etofenprox, 8.78% **w/w** s-methoprene, 2.31 % **w/w** pyriproxifen. Substance III contains 8.90% rnethoprene, 2.43% w/w pyriproxifen. Control substance IVA contains inert control substances. Group B3 (n-6) Adults «9 kg) Five applications of substance II



### The animals were observed for clinical signs oftoxicity and dermal irritation for four hours postapplication and then twice daily for the duration ofthe study (14 days post-application). Body weight, body weight gain, food consumption and clinical pathology parameters (hematology and clinical chemistry) were measured at the required intervals.

All animals survived to the end ofthe study. Immediately after treatment, one adult dog in Group B I (IX applications oftest substances IA and III) showed behavioral changes (running, circling). This behavioral change was not considered treatment-related in adults by the sponsor since it was not observed at 5X the recommended dose. Immediately after treatment, two puppies in Group Al (IX application oftest substances IA and II) showed behavioral changes (running, circling). Four puppies in Group A2 (5X application oftest substances IA and II) showed similar behavioral changes after the first application but not after subsequent applications. These behavioral changes are considered to be an adverse effect. White crystallization was observed on the hair tips ofmany adult andjuvenile dogs in the treated and control groups. The application sites ofall dogs in Group B3 (5X application oftest substance II) had an oily or wet appearance. The sign disappeared from one dog on Day + 14 but was present on all others at the end ofthe study.

All adult dogs and puppies gained weight from Day -1 to Day 14. However, mean weight gain in pups in the treated groups (AI and A2) was 15% lower than the control group pups, although statistics evaluating the % change body weight/day show no significant differences between Groups AI, A2, and their controls (CI) with respect to this parameter for the periods from day I to 7, 7 to 14, and for I to 14. The mean weight gain in the treated adult animals (Groups BI, B2 and B3) was decreased (30-99% as compared to the control group). The difference relative to controls was largest in the smaller adult dogs in Group B3 (99% decrease as compared to the control group). Statistics evaluating the % change body weight/day for Groups B3 and their C2 controls show a significant difference (P<0.05) between these groups (with Group B3 showing

Page 5 of7

### reduced gains) with respect to this parameter from day 1 to 7 and from day 1 to 14 (but with no significance for the period from day 7 to 14). Individual food consumption was not reported in grams but by a scoring system (Fc 1 = 

### 0-25%, Fc 2>25-50%, Fc 3 >50-75%, and Fc 75-100%) and it is considered unlikely by this reviewer that the resulting data would be robust enough to show whether a moderate drop in food consumption occurred actually occurred in the B3 (or any) group from day 1 to 7. No treatment-related hematology or clinical chemistry changes were observed.

Seven animals (one adult, 6 puppies) showed behavioral changes (characterized as running and circling) immediately after the first application of the test substance. They were all exposed (applied "simultaneously") to test material IA (8.20% cyphenothrin, 9.8% fipronil, either in combination with material III, 8.90% methoprene and 2.43% pyriproxyfen, for the one adult, or in combination with material II, 55.16% etofenprox, 8.78% methoprene and 2.31 % pyriproxyfen for the puppies). The registrant has provided a comment (letter dated 11 March 2010) from the performing laboratory regarding this response: "Two of six puppies in Al and four of six in group A2 did some running in circles immediately after application. It 

### lasted one or two circles in the pen and then they calmed down. No scratching or attempts at licking. No vocalization

... Our impression was that the puppies were stimulated by the application of a liquid. They got used to the effect ofbeing wet and no similar signs were seen after the following applications

..." However, the response also includes the following: "The question that needs answering is "why only the test item groups"?

... A subjective conclusion was that the test items may have been cold (or felt cold, maybe as a result ofevaporation?). That could be the reason why the pups did not react after the next applications and also why no signs were seen on the skin and why no other changes were recorded

... "

Since this effect was not observed in controls, it has to be considered an effect ofthe test substance. As there were no indications of scratching or licking at the application site, no vocalization, and the puppies calmed down within a short period oftime, it can be considered a minor effect. However, it is recommended that there be a statement on the label noting this effect can occur but the dog should quickly calm down.

The response from the registrant includes a listing ofthe ages ofthe puppies. Group A2 ranged from 73 to 106 days (mean: 87.2), with only two puppies 84 days (12 weeks) ofage or less. Group Al ranged from 79 to 99 days (mean: 91.5), with only one puppy 84 days (12 weeks) of age or less. Group C 1 ranged from 91 to 106 days of age. It 

### is recommended that the proposed label treatment age be raised from 12 to 13 weeks (or to 3 months).

It 

### is concluded that although there were possible effects, which consisted of short-term running and circling in 2/6 IX and 4/6 5X puppies

- not seen in their controls

- following the first application of the test material and reduced weight gains in 5X adult dogs, these

were minor. In particular, there were no indications that the puppies were in any pain or distress, and a similar response was not seen in those animals in which there was reapplication. It 

### is recommended that there be a statement on the label noting that the puppy or dog may have a short-term response.

Page 6 of7

### This companion anipJaI safety study in male and female random-source adult dogs and puppies is reclassified as Acceptable/Guideline 

### and does satisfy the guideline requirement for a companion animal safety study (OPPTS 870.7200) on 4-20 Ib dogs for a formulation containing 55% Etofenprox and 2.2% Pyriproxyfen with the proposed dosage rate of2.0 mL with retreatment at monthly (30-day) intervals.

COMPLIANCE: 

### Signed and dated GLP, Quality Assurance and Data Confidentiality statements were provided for Clin Vet International. Pathcare Veterinary Laboratory, which conducted the hematology and clinical chemistry analyses, is not GLP accredited but is ISO 15189 certified.

Page 7 of7DP BARCODE No.: 037674" File Symbol No.: 2517-RGG PRODUCT '-lAME: Etofenprox INylar Spot-On Flea and Tick for Dogs & Puppies COMPANY: Sergeant's Pet Care Products Incorporation

DATE OUT: 291 APR 12010

SUBJECT:

FROM:

TO: FEE.PRODUCT CHEMISTRY REVIEW OF MP [] EP [X] FOOD USE [] NON-FOOD USE [X] INTEGRATED FORMULATION [] PCC: 128965 & 129032 DECISION No. 420097 ACTION CODE: R310
Shyam Mathur, Product Chemistry Team Leader Technical Review Branch/RD (7505P)

Kevin Sweeney 1Richard Gebken, PM 10 Insecticide Branch 1 RD (7505P)

INTRODUCTION:

The product chemistry data cited for the proposed end use product was reviewed previously (see PCR dated February 1,2010. DP371682) by TRB and the cited data was found not acceptable. TRB also concluded that the proposed product is not identical to cited product with Reg. No. 69332-3 from product chemistry point of view. The registrant was asked to provide product specific (group A & group B) chemistry data for the proposed end use product.

After conversation with the Agency, the Registrant on April 28, 2010 submitted the revised product chemistry data with MRID Nos. 480584-01 & 480584-02 corresponding to group A & group B guidelines respectively. The registrant also submitted a revised basic CSF (dated April 28, 2010). TRB has been asked to determine the acceptability of the product chemistry data submitted for the proposed end-use product and determine the acceptability of the proposed revised basic CSF dated April 28, 2010.

SUMMARY OF FINDINGS

1. The proposed end-use product contains
, containing of etofenprox] and containing pyriproxyfen] as the active ingredients with label claim nominal concentrations of 55.0% and 2.20% respectively.

2. The proposed CSF for basic formulation (dated 04-28-10) is filled out completely and correctly. The nominal concentrations of the active ingredients concur with the product label claim nominal concentrations. The CSF is in compliance with PR Notice 91-2. All the inert ingredients present in the formulation have been approved by the Agency for the proposed uses (IIAB, 04-29-10).

3. The standard certified limits have been proposed for the active ingredient and for the inert ingredients which are in compliance with the standard certified limit table set-forth in 40CFR§158.350(b)(2). The data submitted corresponding to guidelines 830.1550 (product identity & composition) and 830.1750 (certified limits) satisfy the product chemistry data requirements of 40CFR §158.320 and §158.350 respectively [MRID No. 480584-01].

4. The data submitted corresponding to guidelines 830.1600 (description of material used to produce the product), 830.1650 (description of formulation process), 830.1670 (discussion on the formation of impurity) and 830.1750 (certified limits) satisfy the data requirements of 40CFR §158.325, §158.335, §158.340 and 158.350 respectively [MRID No. 480584-01].

1DP BARCODE No.: D376745 File Symbol No.: 2517-RGG PRODUCT NAME: Etofenprox /Nylar Spot-On Flea and Tick for Dogs & Puppies COMPANY: Sergeant's Pet Care Products Incorporation

5. The product chemistry data cited corresponding to guideline 830.1800 (enforcement analytical method) satisfy the data requirements of 40CFR§158.355. The GC-FID method was used for the determination of the active ingredients Etofenprox and Nylar in the formulated product using internal standard quantification technique. The method employed HP-1 Methyl Siloxane Capillary column, 25 m x 200**~m** x 0.11**~m** (particle size). Dibutyl phthalate was used as an internal standard [cited MRID No. 461613-01].

6. The product chemistry data submitted corresponding to the guidelines 830 series group B (physical-chemical properties) satisfy the data requirements of 40CFR §158.31 O(e), except for the guidelines 830.6317 & 830.6320. The registrant stated that the studies corresponding to the guidelines 830.6317 (one year storage stability) & 830.6320 (corrosion characteristics) will be submitted on completion [MRID No. 480584-02J.

CONCLUSIONS:

The TRB has reviewed the revised product chemistry data submitted for the proposed end-use product and has concluded that:

1. The proposed CSF for basicformulation (dated 04-28-10) is acceptable and will supersede the basic CSF (dated 09-10-09).

2. The data submitted corresponding to guidelines 830.1600 (description of materials used to produce the product), 830.1650 (description of formulation process), and 830.1670 (discussion on the formation of impurity), 830.1750 (certified limits) and cited 830.1800 (enforcement analytical method) are acceptable.

3. The product chemistry data submitted corresponding to guidelines 830.6302 (color), 830.6303 (physical state), 830.6304 (odor), 830.6314 (oxidation/reduction), 830.6315 (flammability), 830.6316 (explodability), 830.7000 (pH), 830.7100 (viscosity) and 830.7300 (density) are acceptable.

4. The registrant must submit the results of studies corresponding to guideline 830.6317 (1 year storage stability) and 830.6320 (corrosion characteristics) which are under progress. It is recommended that the observations should be made at 0, 3,6, 9, 12 months intervals.

2DP BARCODE No.: 0376740 File Symbol No.: 2517-RGG PRODUCT NAME: Etofenprox lNylar Spot-On Flea and Tick for Dogs & Puppies COMPANY: Sergeant's Pet Care Products Incorporation

Product Chemistry Data (Series 830 qroup A & qroup B)

Subgroup A Data Reguired MRID No. Fulfilled

830.1550. Chemical Identity (proposed basic CSF) A 04-28-10

830.1600. Beginning Materials A 480584-01

830.1650. Formulation Process A 480584-0t

830.1670. Discussion of Impurities A 480584-01

830.1700. Preliminary Analysis NA

830. t750. Certified Limits (basic CSF) A 04-28-10

**830. tBOO.**  Enforcement Analytical Method A CITed 46t6t3-01

Data Reguired Value or Qualitative MRID No. Subgroup B Fulfilled Descrigtion

830.6302. Color A Light yellow 480584-02

830.6303. Physical State A Liquid " " "

830.6304. Odor A Sweet mild floral " " " fragrance

830.63 t4. Oxidation/Reduction Action A None " "

830.6315. FlammabilITY A t99.94'F (>93.3 'C) " " "

830.6316. Explodability A Non-explosive " "

830.6317. Storage stability I t year in progress " " "

830.63t9. Miscibility NA

830.6320. Corrosion Characteristics I t year in progress " " "

830.632t. Dielectric Breakdown Voltage NA

830.7000. pH A 9.35 @ 25'C " " "

830.7 tOO. Viscosity A 39 cps @ 20'C " "

830.7000. Density A 1.035 glee @ 20'C " " "

830.7520. Particle size, fibre length, & diameter NA distribution

Explanations: A =The Requirements Were Fulfilled; N =The Requirements Were Not Fulfilled; NA = Not Applicable; G = Data Gap; U - Requires Upgrading; I = Incomplete or In Progress; W = Waived.

3

### Efficacy Review

Date: April 23, 2010
Efficacy Reviewer: Clayton Myers, Ph.D., Entomologist, RD-IB**~~2-""'·IO**



### Risk Manager Rev.: Kevin Sweeney

Products: EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies

EPA Reg. #: 

### 2517-RGG

A.I.'s: Etofenprox (55.0%), Pyriproxyfen (2.2%)

Decision #: 

### 420097

DP#: 376747

Submission: Rebuttal, correspondence

MRIDs: None

GLP: No

Summary ofAgency's previous product performance review(s):

I. 

### Various studies were submitted in support ofa pet product with a retreatment interval of 30 days, intended to protect small dogs from fleas and ticks. The data submitted did not support this claim, because at the appropriate dosages (which match the label dosages), efficacy was only demonstrated for 2-3 weeks for fleas and ticks, with some variability between studies. 2. Ultimately, the underlying conclusion ofthe data is that a 250 mglkg 

### dosage is required to provide adequate protection against fleas and ticks. For the most part, dosages under this threshold failed to offer adequate protection throughout the 30 day retreatment interval 3. Claims against black legged ticks (deer ticks), Ixodes scapularis 

### were only supported by data going out to 3 days after treatment. 4. Claims against mosquitoes were not supported as the submitted study treated dogs at dosages exceeding those instructed on the product label. 5. Claims against flea eggs/larvae were not supported by any submitted data for pyriproxyfen.
Summary of Registrant submission/rebuttal:

### 1. For flea and tick data all data from dog studies was pooled and re-analyzed. When dogs that received treatments above the proposed label dose (i.e., >2.0 mL per animal) were eliminated from the analysis, flea efficacy was demonstrated from 9-29 days, with a
mean protection time of 20 days. Out of 18 dogs, 11 were adequately protected for 16 days or less. For tick efficacy, the mean protection time was 26 days. Out of 18 dogs, 10

were protected for 23 days or less. 2. For mosquitoes, the registrant stated that only small dogs were used (hence, biasing the dosage toward dogs with a higher rate ofai/kg) because the available Gerberg type mosquito cages were not large enough to accommodate dogs ofiarger size. The registrant cites previous reviews where similar data was used to support a similar claim, including dogs over 60 lbs. Finally, while they concede that a controls or kills claim is not supported, they propose to retain a claim ofrepellency/prevention ofblood feeding by female mosquitoes. 3. For black legged ticks, the registrant cites a previous protocol that was used to support a 30 day claim on another label, and proposes a retention ofan open-ended controls claim for black legged ticks, since no explicit '30 day' claim is being proposed. 4. For the pyriproxyfenlIGR claims (i.e., kills flea larvae, eggs, breaks flea life cycle), the registrant cites previously submitted data that supported a similar claim on a product containing a smaller nominal concentration ofpyriproxyfen a.i. than the submitted product.
Entomologist's ObservationslDiscussion:

I. The registrant's ultimate conclusions after re-anaylsis do not substantially differ from the conclusion reached in the previous review. At a 2.0 mL dose, efficacy against fleas is supported for 2 weeks and ticks for 3 weeks. Because this product's use directions indicate retreatment on a 30 day interval, the implied duration for all control claims should be 30 days. In order to support a 30 day claim, the registrant would have to increase the dosage applied, based on the data submitted previously, which indicate that a dose ofapproximately 250mglkg is necessary to provide adequate 30 day control ofboth pests. 2. The availability ofmosquito cages is a consideration that should be taken when designing efficacy studies. A number ofmuch larger mosquito cages are available for conducting these types ofmosquito exposure studies, as the Agency has reviewed data where significantly larger dogs were used for similar studies. Prior acceptance by the Agency ofinadequate data to support such claims is not an adequatejustification to repeat the

same mistake again in this instance. 3. Open-ended controls claims are typically not allowed on any pesticide product with claims against pests ofpublic health importance. Any claim ofresidual control must be qualified by an appropriate duration ofcontrol that is supported by the submitted/cited data. In the case ofa pet spot on, the retreatment interval is considered an implicit duration ofcontrol claim. Consumers buying this product, and treating their pets on a 30 day retreatment interval will expect the product to adequately protect their pets for that intervaloftime. Therefore, data demonstrating control ofblack legged ticks for 30 days would be required to support a controls claim on this pet product. Since the submitted study was terminated at 3 days after treatment, it does not support such a claim.Furthermore, as with point number 2, prior acceptance by the Agency ofinadequate data to support such claims is not an adequatejustification to repeat the same mistake again in this instance. 4. The dose-titration study cited (MRlD 46346601) submitted in support ofa similar IGR claims on another product and was found to be acceptable. This study supports IGR claims (i.e., kills/controls flea eggs and larvae, breaks the flea life cycle, etc.).


### Entomologist's Label Recommendations:

1. Placement of2 or 3 week claims on the label (for fleas and ticks) would be contradictory to the reapplication directions for 30 days. For such pet products, a 30 day retreatment interval implies a time duration for control oflisted pets. In this case, efficacy considerations may be in conflict with animal safety. This labeling decision is deferred to the Risk Manager Reviewer and the Product Manager. 2. Claims against Mosquitoes are not supported for the application rate of2.0 mL proposed

on the current label. The dosage would have to be raised to support this claim, and the claim would only be for repellence/suppression ofmosquito blood feeding. These claims must be removed from the product label. 3. Claims against black legged ticks, deer ticks, 

### Ixodes scapularis, or ticks that may carry/transmit Lyme Disease are not supported and must be removed from the label. 4. While IGR claims are supported against flea eggs/larvae, the acceptance ofthis claim is contingent upon whether or not any general flea claims will be allowed at all, per point number 1. This labeling decision is deferred to the Risk Manager Reviewer and the Product Manager.April 29, 2010

Richard Gebken Product Manager 10 Document Processing Desk Office of Pesticide Programs (75041') U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South CJystal Drive Arlington, VA 22202-450 I
Subject: Submission ofa Response to EPA Regarding Etlicacy and Labeling Etofenprox/Nylar Spot-On Flea and Tick I'or Dogs and Puppies (25 I7-RGG)

Dear Mr. Gebken:

On behalf ofour client, Sergeant's Pet Care Products. Inc. (Sergeant's), Exponent is providing additional information in response to a telephone call with Kevin Sweeney dated April 29, 2010 regarding ellicacy data and proposed labeling telf Sergeant's Etofenprox/Nylar Spot-On Fica and Tick Products for Dogs and Puppies (EPA Filc Symbol 2517-RGGl.

Based upon our discussions it is Sergeant's understanding that the available efficacy data Oil file with EPA for etofenprox support etlicHcy claims against fleas and ticks it)r four weeks when a dose of::::250 mg/kg is achieved. Therefore, Sergeant's proposes to change the current pending label that proposes a single 2.0ml dose for dogs weighing 4-20 pounds to two di ITerent proposed doses. The new proposed doses t(lr do gs are:

4- I 0 pounds: 2.0 ml 10-20 pounds: 4.0 ml

Based on the above dose configurations, Sergeant's confirms that all dogs will receive :::250 mg/kg ofetofenprox, which will allow Sergeant's to claim t(lLir week efticacy on the product label. Please see Enclosure I tor a summary table that identities the calculated amount ofactive ingredient per pound ofdog and a comparison of the dose versus the companion animal safety study (CASS) rates. The summary table confinns that 2.0 ml applied to 4-10 pound dogs applies 636.6-254.6 mg/kg, respectively and that these rates are well within the I x CASS rate of 689.7 mg/kg. It also confirms that 4.0 ml applied tol 0-20 pound dogs applies 463.0-254.6 mgfkg, respectively and that these rates are wcll within the Ix CASS rate of689.7mg/kg.

Based on this information we have updated the proposed product label to include the tollowing:

• Two application sizes (2.0 and 4.0 ml) and corresponding label language;

• Changed the age ofpuppies from 12 weeks to 13 weeks:• Added four alternate brand names:
• Increased the efficacy claims for fleas and ticks to four weeks (30 days); and

• Added proposed language warning of possible temporary effeels (see helow for proposed language),

Based on our discussion today with EPA. Sergeant's has added the following proposed label language:

"[Some dogs may startle when a room temperature squeeze-on is applied.]fSome dogs may experience temporary startle effects when a squeeze-on is applied,][Somc dogs may experience temporary startle effects when squeeze-an's arc applied.

# r

We believe the above language addresses EPA's concern related to the possihle effects noted in the CASS study.

Please tind enclosed a copy ofthe new proposed label in track changes (Enclosure 2) and a copy with all comments accepted (Enclosure 3).
Sergeant's requests that EPA review the new proposed label and supporting summary tahle and in support ofthe registration ofSergeanfs EtofenproxiNylar Spot-On Flea ,md Tick Products tc)r Dogs and Puppies.

I

## ryou have any questions or'need additional injormation. please contact me at 202-772-4932 or 30J-908-J J8J (cell).
Sincerely. 

# I

! James Messina Authorized Representative of

. Sergeant's Pet Care Products. Inc.

Enclosures

cc: Kevin Sweeney. EPA Kelly Hoskins. Sergeant" s Larry Nouvel. Sergeant" s Rick Tinsworth. Exponent

--"""'Enclosure I
Dosage Chart for Sergeant's Proposed Etofenprox-Containing Squeeze-On Lahel for Small DogsTABLE3DosageChartforSergeant'sProposedEtofenprox-ContainingSqueeze-OnLabelforSmallDogsJustificationExtrapolationfromCASSCV0855DogweightActiveEtofenproxCASSdosePyriproxyfenCASSdoseLabelpotency55.0%ratefactor2.2%ratefactor@UCLofCSF57.8%1X5X2.3%1X5Xpuppies689.73796.3·28.91590adults1759.02.111.0IbkgmLmg/kg41.82636.625.552.32509.320A62.72424A17.073.22363814.683.62318.312.794.12282.90.1611.30.07104.52254.60.1410.20.06115.04463.00.2618.50.12125A4424A0.241700.11135.94391.70.2215.70.10146A4363.80.2114.60.09156.84339.50.1913.60.09167.34318.30.1812.70.08177.74299.60.1712.00.08188.24282.90.1611.30.07198.64268.00.1510.70.07209.14254.60.1410.20.06PotencyisuppercertifiedlimitonConfidentialStatementsofFormulaeallothersbasedonadultCASSmeangroupdoserates

## Sergeant's Pet Care Products, Inc. Master Label i-.'!**<:\PDL~~}Ji1** EPA Reg.. Nn,**2517~j{{_;_(_~** Information in I I is optional. Page I 01'4 EPA SAL FRONT PANEL DOG SQUEEZE

- ON Pyriproxyfen (NVLARj, Etofenprox Edltor$ NOh:" {Optional proposed leXI appears In**bra.::~cls** the final label**tna~** Include "ome Of atl of the optlonallcxl!
ETOFENPROX/NYLAR SPOT-ON FLEA AND TICI( FOR DOGS AND PUPPIES
{ABN: Sl."fgcanfs Toy Br.:cd Flea and Tick Squeeze-On I {ARN: Sergeant's Toy Breed Flea and Til:k Sqllceze·Qn lor small ore-cd dogs) {ABN: Sergeant's Toy Breed Flea and Tick Squce7C-0n for small and toy breed do!]..<;) {ABN: Sergeanrs Small Breed Fica and Tick**Squcezc~)nJ** rABN: Sergeant's Small Breed Flea and Tick Squcezc·.()n for small breed dogs} {ABN: Sergeant's Small Breed Flea and Tick Squcezc-On for small and to), breed dlJgs} {ARN- SentryPro Toy and Small Breed Flea and TIck Squeeze-On}**~** ABN: ScntryPro Toy and Small Breed Flea and Tick Squeezc-On ror dngs I \ARN: SClltryPro T(lY and Small Bn,"Cd fica ilnd Tick Squeeze-On filr small and toy breed dugs] {ABN' SentryPro Small Breed Flea and Tick Squcc7c-On for IAlgsj j AnN SemryPm Small Breed Fka altd Tick Squee:rc-On filr small brl!cd dogs 1 tARN: SentryPro Smail Breed Flea and TIck**Squee7~,**.. On ror smail and OJy br\..-'Cd dogs) l \i{,\ \crgl',Ill(" Ii I \**,d\:,,'_~-::i** .[.1**l~"l** All,J J ;,.:h \lilJ..:C/;:-I.)1l i(,r !**Id~"- L,~nd**  PIolPPk·\.!;
: ·\il:,_ \<:rgl.':[Il{**~J;.** J_ \,'-'\.c U Ii!. I il',) ;llIJ Ixk \(!ii\.:Ch'-}}f! 1;'1_1 )llS-'-**('lll~** PIIPPI\."!;**~**__**ll}_~_~~;:_LUr';.tr -'--~_~_**  i.L.l**L_di.Lki.l.;W!J.J_!!'_~ _2~l!i<;.l:** **;:~«** .1)1 I,

..'I .•1),**~"o~.** !.c@!L'!!l!1?J**~.~ i~** **l.:\H~~.** )S.llll**lj)i.;.~._SULiJDJ1J!-!.;I.Ar\\lJ_!,,·k_. ':~lm·\.~~~:(** __I.1.1 J!.!£

..P:'2.':**L~! ~dJ** **)1'l'I'IC'~** .'

lOne Applicatinn:{choose frnm the followillgJ!

•**[\~itb** nylar)q HOnc) (Two) (Three) (Follr) (XX) Appileations] IBonU$]**J.'i~';,** mme lmlw incJtldes 4 tuhcs! lodorlessl Junsccnlcdj iIragranec freel lDries quickly] 1(>tJick drying formula I [QUIck Dryingl [Squeczco·Oullstays on and dnesn°t rub 0111 ISpreads b)' tising the dog's natural skin oilsj

• IBreaks thc flea life cycle fi)r up to (70 Days) (9 Wceks)j

• lControls rcinfcstalion fhr up to (7f) da)'5) (9 wCl!ks)! [For Kly breeds 4-.LO Ibs.] IFor small br\..'CdsJi'-20 Ibs,]

• [For toy and sOlall hrct:dsI4-1(IHlii-20j Ibs.l

• [Specially lonnulatcd fbr small hrecdlsl dogs I

• [Spccmlly fonnulated for toy brccdls] [dogsl] ISpcclally fimnulatcd lor [tny breedls]I and**l~mall** breedlsll dogsl lToYllandj [SOlal!] hreed ronnula] rCcntle protection fiJr [toy] [small I breed dogsJ

• 15 Way Protectionl

• lControls Ilea'>, ticks, flea eggs & larvael IKills FI':llS, Ticks, !--lea Eggs, Larvae] [and IIrepels mosqllitoes jfi.lr up to olle month J [fi}r up to 4**~t-eeks**JJ

• Wka, tick, nell. cgg and larvae controll

• lKills Ilea'> aud ticks for up to L'fl days]l.:-i weeksll
• f"-ills ticks [for up to**~,I)** daysj 1.:-1 wceksl1]
• JKiIls TicksJ [Berore they can} JthatJ [transmIt Lyme Disease [Kills laduJt] fleas for upto IJ!.; daysl!.:! wecksJ]

• [Kills**Flca~** and Ticks] Jfor up to k"iil daysl!;1 weeksl]

• [Fica Tick and Flea Egg ProtectionJ • IRepels mosquitoes Iror up to one montJJ] ] lor up to 4 -'>-'.'Ccksl! IFka and Tick**~'{)ntrol**J

• [Kills Ilea'> that may cause flea allergy dermatitis, and flea bite anemiltJ Ifbr up to**I,:~(I** dayslll \\-eeks]] • ]Kills Flea Eggs and Larvae Ulr up to (9 weeks) ( 70 days) (per appilcatlOn)1 I Detebed: 10
Delel2d:**S,"!I~"ll1~_~O,~,.** Deleted: xx

Defeted: "2 Oefeted: 4

Deleted: 21 Deleted: :> Deieted: 11 Deleted: 3

Deleted: 2t
Deleted: 3 Deleted: 21

## Sergeant's Pet Care Products, Inc. Master Label
"."-'J**~ WnL_~QEi**  EPA. Reg No.**2517~!~(_J(!.** Ini(!rmatioll in I I is optional. Page 30(4 EPA SAL

BACK PANEL DOG SQUEEZE-ON Pyriproxyfen (NYLAR), Elofenpro. 

### {Product Name} REAl)**E~TlRE** LABEL BEFORE E,KIf**[S~:** PRECAVTIO:,\,,,RY STATElHE:\TS HAZARDS TO**H[l'IA~S** AND DOMESTIC ;\1\I\1..\I..S CAliTlON

JIAZARDS TO II**{;:MA~S:** Causes moderate eve irritation. Avoid contact \vith eves and clutlrim.!_ W;l<;h thoroughly with soap and water after haJldlmg**~d** ix=ij)rc eating, drinking, chc\.\illg gum, or using'i()hacco.

HA7ARDS TO DO.'1ESTIC ANI\IALS: F,)r External Usc On!} Do no! usc on dogs under 1..-: weeks of age. (,onsult it veterinari:m bel()fC using this prnduc! Oil debilitated. aged. mcdicatcd. pregnant. Hr nursing anim:dj; SensitivitIes may (!CC{lf ailtr**U~lng** ANY pesticide product for pets, [fsigns orscllsitivit) occur, hathe your pet with mild soap and rinse with large anroullts ofwater If signs continue, conSilII a \-dcrillllrlan Immediately_**llW~** -,,;)flk \'iH.:n ;. ",;\'Ill \(liiI'CI ;i!li,C**"'lHC~·/<:-'·H.** I- "PP(lc-ci it'.,!**'!11~'** ), '.ie-**:1!;I~,** ..:\j1<.:r;':Il(C kllif','r;Jf:'. """I"'JJ,,i'.""'"'L'''''''''':''':'J', ,'J'T' "" ,JL"!''Ie.'."'],**!IF\~ "·'II~'J** **~C.;.I":l·** t_':!.i:'f':.'f:il). ,:1**~lnk** ..:111'<\**,:.\\!.~C.I.l. _,:q!!U;/~·.:**  "\1. '- .;()';_**~!l~~\ I,~\t**  J

FIRST AI[)
IF**I~** EYES: Hold eye open and rinse slowly and gently with Water filr**15~20** minutcs. Remove contact lenses, Ir pn

.. "'SCnt. after the first 5 minutes. and thell continue rinsing. Call a POi$(lO cOnlTOI center or doctor for treatment advice Ilavc the- product container or labcl l\ith YOll when calling a poison cuntrul center {Ir dOl-1m or g\)ing for trea(ment. Ynu m:ly also contact 1-800

..781-4738 1(lr emergency medical treatment infiJrmation.

PI-IYSICAL OR ClIEMICAL HA7ARf)S: Combustible; 1)(1 nil! use or St{lrc ncar heat or Opell namc.**OIRECTIO~S** FOR [Sf: It is a violation of Frderal Law to usc this product in a manner incon!iistcnt with its labeling.

Do nHt get this product in your pet's eycs or mouth, Do Hot apply more otlcn thaJl lom.:c a month Iionee**ev~ry** 30 daysl tlse only on Dogs. FOR EXTERNAL CSE ON DOGS ONLY Do not usc on puppiesle!is than l.' ',>,'1.:cks ofage. Weigh your dog !H he sure Y(Hl are applying the right dose lormulated for thc weight Ill'yuur pct. Do nOl trC<lt your pet with more than one pesticIde pwduct at a rime. Over dosmg your wlimal can result in serious illucss ami even death. Best ifuscd ycar round. 00 not bnthe pct with In the ftrst 24 hours aticr squce7e-on ha<; been applied. ff(lUscholds \\ith more thmlllnc pet should no( allow dogs (Ir cats to groom each other until solution has dried. DO NOT USE ON CATS or ammals other than dogs. Separate the treated dog trum all other dogs and cats filr 24 hOllIS aftcr treatment has been applied. Cats or dogs that actively groom or engage in dose physical contact with treated dngs oray be:lt risk orsenous harmful elTccl<; Iryour dog is exhibiting signs o/'and/or arc being treated for skin dermatitis. talk to your vet before applying any topical flea and tick control product. Sensitivities ntayoccur after using ANY pesticide product on pets. It )s recommended to separate treated dogs from other household pets for 24 hours after treatment**ha~** hcen applied. Ifsigns of sensitivity occur. bathe YOllT d{'g v.r1th mild soap and nnse \\-ith large- amounts of\vater.

FOR liSE 01\ DOGS: Wt'ighing 4 T0.t0 I,BS.

- Apply contcnts ofone (2,0 mL) tube Ina!} oflProduct i'ameIlSqueeu-tlnl as a spot high on the back ofthe dog's ncek behind it" head and apply as a stripe to a POlOt mid\\-ay between the neck and the tail ! Deteted: 10**I"_~: ~~!~::b:,!}{)0')**  \ Deleted: XX ,

Deleted: 1

Deleted: 2 I

## Sergeant's Pet Care Products, Inc. Master Label**,,:()~'\nrJL;UJn** EPA Reg. No,**2517-F(,()~** In(bmlut}()}) in 

### t J is optionaL Page 2 of4 EPA SAL
!'Prcvcnts flea eggs from developing into biting adults for up to (9 weeks) (70 days) (per application)]
• lRcpcts mosquitoes that may tran<;mit rhc-artwoTm} [Wes\ Nile vlruS! [from fcedmg on dogs1 I for up to [one monthJ pO daysJ[ 4 weeksll

• p<epels MO$quitoesJ IPrevent.:; mosquttoes that tJdnsmit West Nile viru..;; and heartWOmll1 from feeding on dogs]**[t~)rlIP** to lone momhl pO daysJf 4**weck~JJ** FRONT PANEL DOG SQUEEZE-ON Pyriproxyfen (NYLAR). Etofenprox

ACTIVE INGREDIENTS: Ewfenprox, Pyrirroxylcn

.... OTHER INGREDIENTS:. 55.Q()O/o 2.20 1 %**1~Jli~Q** fOO.OO% TOTAL
INyJarK is a reg"!stered trademark of ,\kLaughlin Gonnky King Company!

KEEP OUT OF REACII OF CHILDREN CAUTION See IBackl!orliSidel Label PanellsJ for Additional Precautionary Statements

NET**CO~TE:-';'rS:** [Om'j jTwoljThreejjf'ourjjFivcj [Six I 2,0 mL. applicators. Uor small dogs 4 to.1.0 lh.\'!
lii.llt'l ! 1**\\o!11Il1'{'{'I!I'1)}il'!!HH!f~i\!** .t.n 1111**applit~\t()r'** .... W,r \I1wll dOt:\ {fl Io J(j 11>\1 Dcleted: 10
0eJet:ed:.**S~lembe12009** Deleted: xx

## Sergeant's Pet Care Products, Inc. Master Label 

# I
,;>!**/~N.!l.~_(lj(l** EPA Reg. No. 2517'T{(**J5_~** 

## !

Inlomtation ill 1 f is optional. Page 4 of4 EPA**~~_"**__**~~**__**~** (INSERT**DIAGRA~1** THAT DEPlers APPLICATIO'i Of PROOFCf**O~** l'UE DOG)
H)H r:-.r 0\ 00(,:--: \\ (oj"hi!l(t Iii TO 2(1 I**Jj.~~)h .~~:E.!:.~!..'{...:.:L~L!.!!LlJi!.!::~.L:_,:!..!:1** **,~Jlr.U!ili~r.!_~,!!!.fJlSi1~!_t:Y_£:,"~!lL!..':._;!_::i2~\'** hl,\}<,r;.l1 Ih",**b~!~-L** ;," 1)1<.: )'-'.!s';. 11\.:.:), h,'\)\\1(3 I\'. l)"'.',t(j .1:1(: ;\1']'):' ,j, a ,t) T': 1 .\ pl>Jm. T!!id".;.1.; 11c'",:.::":1\ tho: w:"t. ;'1:"**:!!~­** '<Iii LL'\SLRT DL\(, rt,\ \1 nl \.T nu'j( T'I \I'I'I.IC \T!O

.... 01-**PIH)lg.J...:L~L~lJ.J.L~~_Qiil**
HOW TO ;\PPLY: Relllove prodUL1 tube {VIal} frOnllhe packag.e. Holding lube /\'/0//**~",ilh** ntJlchcd cnd pointing up and away from the face and body cut or Icar ofl'jhe naml\\' end at the nOlt.:'hes. While holding the animal with one hand. usc dIe OIher hand tn apply the solUlion. Invert the lObe {vlalj and (1St' the narrow end 10 part the anintal's hair**whik~** gently :;qucczjng to apply to the animaf"s skin. Iiold the animal for a fcow seconds to give the solution time til be ahsoro.::d illw thc animal's coal. When finished. \\Tap the tube jVJaI! in paper and put into lhe tra"h. Deleted: 10

## Sergeant's Pet Care Products, Inc. Master Label ':_::.:-'Dr))

__**J:PJ~1** EPA Reg. No. 2517-l<t,I(>, Illfomlation iul I is optional. Page 5 of4 EPA SAL BACK PANEL DOG SQUEEZE

- ON Pyripro.yfen (NYLAR). Etofenpro.

STOR",GE**A~D** I>ISPOSAL Du not cOlltaminalc waler. food or feed**h~** s.hlragc llr uisposnl. PESTICIDE STORAGE: Do not remove tube from the pack until ready 10 USc, SWrc in a cool (bdtW, 25"C) dry place out ofrcach ofchildren. 00 not refrigerate Protect from direct sunlight.

PESTICIUE DISPOSA L; Nonrefillable container. Do not reuse or refill tillS container. OJfer for**rec~cling** or n."COnditioning, ifavailable and appropriate. Ifempty: Do Hot reuse tbis container Place in trash or offer for rccycling ifavailahlc. If partly Oiled: Call your local solid wa<;IC agency f{lf dispos.!ll iostructions. Never place unused product do\\'n any indoor or oUldoor drain.

IWARRANTY Rcad the entire Directions for Usc and Warranty before using this Product. By usiog this product. user or huyer accepts the following warranty. Ipne directions for usc ofthis produl.-1 arc believcd 10 be adequate and must be followed carefully. fIo'wever, it is impossible to eliminate all risks inherently associated with the use ofthis product Unintended consequences may result because ofsuch facton; as weather conditions. presence or absence orother materials. {lr the manner ofapplication, all ofl\"hich are beyond the control ofSergeant's Pet Care Products. IneJJ Scrgeant's Pet Care Products, Inc. is ctlmmitted to providing higb quality products To the extent consistent with applicable 11'1\\'. Sergeant's Pct Care Products. Inc. makes no warranties. expt\'·ss or implied, ofmerchantabihty or of fitness fhr a parth

.. l.llar purpose or othemisc. that extend beyond statements on this label. To thc extent consistent with applicable law. Sergeant's Pet Care Products. Inc., the manuf.'lCtut"er. or the Seller disclaims any liability whatsoever for special. incidental. or consequential damages resulting front the usc orthis product. To the extent consistent with the 13\\. the cxcltL"I'ie**rl!mcd~'** ofthe user or buyer sha" npt exceed the purcha'>C price paid.!
(Sergeant's Care Pet ProduelS, Inc. is committ<::d to providing hIgh quafit) produCl,\. I(you have queslions or IXlmlllcnts anout this product. please \\Tite; Sergeant's Consumer R!...""Sponsc. P.O. Box 540399, Olllaha. NF (18 I54· 03991

In**Ca~c** ofF.ntergcncy. call: I-ROO-781-4738 Non-Emergcncy call: 1-800-224-PETS (7387)

Distnbuted by:
Sergeant's Pet Care l>roducl". Inc. PO Box 540224 Omaha. NE 681 54 lEND

- BACK I SlOE PANEL}
TUBE I VIAL LABEL (For more**inlormallonllVi~it Il~**  tlt! \i. ,\ \\**~c:rg~';lIlh** ,', m Made in liSA

EPA Reg. No. 2517-XX EPA Esi. No. >..'XXXXXX {date & lanel CQdcj

Fr_on_t_L_._be_I_.

_____________ -iB7ack Label {product Name}

. . I KEEP 01 T OF**Rl'~ACH** OF**CHlI.l)Rf~·--l** Etofcnprox

..... ,.. 55.0% W/W i CAUTION Read dlrectinns and pn:cautions beforc i Pyripm.xyfen

......2.2'-;'" W/W Ii LL"ine.. i 2.01LL{U mL label code:**EPA~**REG. No. 25J7-XX {label code} J Deleted: 10 Deleted: Delemd:XXEnclosure 3
Proposed Label with All Comments Accepted

# EXponent"

April 28, 20 I 

### 0

Richard Gebken Product Manager 10 Document Processing Desk Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
Subject: Submission ofa Response to EPA and Supporting Data Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 20036

telephone 202-772-4900 facsimile 202-772-4979 www.exponent.com



### EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies (2517-RGG)

Dear Mr. Gebken:

On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's), Exponent is providing a response to EPA's email dated April 26, 20 I 0 regarding product chemistry and acute toxicology data for Sergeant's EtofenproxlNylar Spot-On Flea and Tick Products for Dogs and Puppies (EPA File Symbol 2517-RGG).

Product Chemistry


### Confidential Statement of Formula 

### Sergeant's originally submitted a basic and alternate (#1) formulation for 2517-RGG in September 2009; however, based on recent EPA guidance, Sergeant's has limited the CSF for 2517-RGG to a single formulation (basic CSF dated April 23, 2010, Enclosure I). 

### Unfortunately the basic CSF dated April 23, 2010 has some errors on it. Sergeant's is now submitting a new basic CSF dated April 28, 2010 (Enclosure 2). The errors that were corrected are with regards to #7,8,9, II, 

### and 12 to match the product specific product chemistry data submitted under MRID 48058402 (please note the study title lists the formulation as "alternate" but this was before we switched to call the CSF the new "basic"). It 

### is the preference of Sergeant's to obtain approvaJ ,., from EPA for the CSF located in Enclosure 2. • , : , )';" , 

# . , 

# .. The following is a comparison ofthe available product chemistry data:**r-------===-------,-------~=-------_,--~~~~~----_,----~~-. }~** 

## f-::-----;-~c:;C~SF";:_--_f----p!:?JH~---+__-...::F:...:I=:as~h:cP:;_o"'i:.::n"-t**_---I~----;;.'. ~3'I'~ms~~** **i-'B=a=s:o.:ic:..c9:.:..1,,-10:::,1.::.:09~-,-,-,-,,----+-** __ ----,2=.,,-3

___ 

## +

__ --,1:...:4.:,-9°:-F=--

__ 

## +-

__**~·~Hb,ilgal~~** Alternate #1 9110/09 2.3 149° F 8.9lbs/gal**~** 

### Alternate#14/9110 9.35 >93.3° C (>199.94° F) 1.035 g/mL "

.. 

## I Basic 4/28110 9.35 >93.3° C (>199.94° F) 1.035 g/mL**~I**

### Please note the data listed above for the two CSFs dated 911 0/09 were based on estimated data. The data listed for the CSFs dated 4/911 0 and 4/2811 0 are based on product-specific data submitted to EPA under MRID 48058402.
EnforcementAnalytical Method In response to EPA's question on what is the enforcement analytical method for 2517-RGG, Sergeant's is citing MRID 46161301. This is the enforcement analytical method submitted to EPA on SPI #8208-55D (EPA Registration Number 69332-3). Both products contain the same active ingredients at the same percentages; therefore, the analytical method is applicable to both products. Please see Enclosure 3 for a copy ofthe EPA review dated March II, 

### 2004, in which EPA accepted this study.

Acute Toxicology



### We have reviewed the available acute toxicology data submitted to EPA under EPA Registration Number 69332-3. The following table provides a surmnary ofthe acute toxicology study results and MRID numbers:
Study ResultslEPA EPA Classification MRID 

### Category 

### Acute oral toxicity >5050 mg/kg (IV) Acceptable 46161303 Acute dermal toxicity >5050 mg/kg (IV) Acceptable 46161304 Acute inhalation >2.08 mglL (IV) Cited 45121105 toxicity Primary eye irritation Mildly irritating (III) Acceptable 46161305 Primary skin irritation Slightly irritating (IV) Acceptable 46161306 Dermal sensitization Negative Acceptable 46161307

Please refer to Enclosure 4 for a copy ofthe EPA DERs dated February 10, 2004.

We then reviewed the basic formulation CSF for 69332-3 (CSF dated March 25,2004) and compared it versus the pending basic formulation CSF for 2517-RGG (CSF dated April 28, 2010, Enclosure E). Please refer to Enclosure 5 for a copy ofthe basic CSF for 69332-3. The following is a comparison ofthe two formulations:
Ingredient 69332-3 (Basic) 2517-RGG (Basic)**~J..-'-L** 

### Etofenprox 55.0% 55.0%

); >},) ),' ; 

### CAS 80844-07-1
, , 

### Pyriproxyfen 2.2% 

### 2,.'{."19

.. ,



# . . , CAS 95737-68-1 ' 

# . "



# . ,}) J

### Please see Enclosure 6 for

a copy ofthe submission and EPA approval letter. This EPA approval was granted without the requirement for additional acute toxicology data on the new formulation.

Further we reviewed available acute toxicology data on the two inert ingredients identified in the table above to determine ifthere was any concern related to each specific inert ingredient. The data were identified in publicly available MSDS. The following is a comparison ofthe available acute toxicology profile:
Study/Species Acute oral toxicity-rat Acute oral toxicitymouse Acute dermal toxicityrabbit
b 

### Refer to MSDS Enclosure 7 2Refer to MSDS Enclosure 8 Comparison 

### Similar Similar

Similar

Based on the above-referenced comparison table, both inert ingredients have a similar acute toxicology profile; therefore, the available acute toxicology data on the basic formula of 69332-3 is representative ofboth formulations. The results are not expected to be significantly different if

new data were generated.

Ifyou have any questions or need additional information, please contact me at 202-772-4932 or jmessina@exponent.com.

lru;erelY, 

# ,,){)1v-:-/

! !

. 

### (J¢nes Messma £;Authorized Representative of Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kevin Sweeney, EPA Kelly Hoskins, Sergeant's Larry Nouvel, Sergeant's Rick Tinsworth, Exponent ,')
,

### Enclosure 1

2517-RGG Basic CSF Dated April 23, 2010

i}
, ';'
,

'))) , ,

### Enclosure 2

2517-RGG New Basic CSF Dated April 28, 2010UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

April 15, 2010

SERGEANT'S PET CARE PRODUCTS, INC. 2625 SOUTH 158TH PLAZA OMAHA, NE 68130-1703

Report ofAnalysis for Compliance with PR Notice 86-5 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES

Thank you for your submittal of 12-APR-I0. Our staffhas completed a preliminary analysis ofthe material. The results are provided as follows:

Your submittal was fouod to be in full compliance with the standards for submission of data contained in PR Notice 86-5. A copy ofyour bibliography is enclosed, annotated with Master Record !D's (MRIDs) assigned to each document submitted. Please use these numbers in 

### all future references to these documents. Thank you for your cooperation. Ifyou have any questionS concerning this data submission, please raise them with the cognizant Product Manager, to whom the data have been released.

# EXponent

April 9, 2010

Richard Gebken Product Manager 10 Document Processing Desk Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
Subject: Submission ofa Response to EPA and Supporting Data 480584·00

Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 20036

telephone 202-772-4900 facsimile 202-772-4979 www.exponent.com



### EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies (2517-RGG)

Dear Mr. Gebken:

On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's), Exponent is providing a response to EPA's memorandum dated February 24, 2010 regarding efficacy and CASS Data Evaluation Records (DERs) for Sergeant's EtofenproxlNylar Spot-On Flea and Tick Products for Dogs and Puppies (EPA Reg. No. 2517-RGG). I will contact you in the near future to schedule a meeting with you and other Office ofPesticide Program's (OPP's) staffto discuss OPP's DERs and the Sergeant's response to the OPP reviews. Please find enclosed the following support documents:

• Transmittal document;

• EPA Form 8570-1;

• Enclosure I. 

### Sergeant's response to OPP's efficacy reviews for MRIDs 47849601, 47849602,47849603,47849604,47849605,47849606, and 47849607. The response provides a narrative discussion and tables ofdata consistent with that discussion;

• Enclosure 2. Revised Sergeant's Master Label for EPA Reg. No. 2517-RGG reflecting claims supported by the rebuttal discussion provided in Enclosure I;

• Enclosure 3. Sergeant's response to OPP's CASS review for MRID 47849609. The response provides a narrative discussion and tables ofdata consistent with that discussion, and also includes a response from the testing laboratory relative to a particular comment made by OPP. Included is Enclosure 3 Attachment A;

• Enclosure 4. Copy ofEPA efficacy review;

• Enclosure 5. Copy ofEPA CASS review; and

• Product-specific product chemistry data.

### Ifyou have any questions or need additional information, please contact me at 202-772-4932 or jmessina@exponent.com.
Sincerely! 

### / "'1'
, ( ,J ['i \;**(i~ '~'I-f**  [/ --" I 

### Jmhes Messina ,J(uthorized Representative of Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kevin Sweeney, EPA Kelly Hoskins, Sergeant's Larry Nouvel, Sergeant's Rick Tinsworth, Exponent

### Data Transmittal Document:

Product: Sergeant's EtofenproxfNylar Spot-On Flea and Tick for Dogs and Puppies 2S17-RGG

Submitter: Sergeant's Pet Care Products, Inc. (EPA Company Number 2S17) 2637 South ISSth Plaza Suite 100 Omaha, NE 68130-1703

Return to: James Messina Exponent IISO Connecticut Ave., NW Suite 1100 

### Washington, DC 20036

Submittal Date: April 9, 2010

Volume Study Title I Group A Product Chemistry for EtofenproxfNylar SpotOn Flea and Tick for Dogs and Puppies (Alternate) 2 Group B Product Chemistry for EtofenproxfNylar SpotOn Flea and Tick for Dogs and Puppies (Alternate) MRlD
48058401

48058402

# EXponenr

April 9, 2010

Richard Gebken Product Manager 10 Document Processing Desk Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
Subject: Submission ofa Response to EPA and Supporting Data Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 20036

telephone 202-772-4900 facsimile 202-772-4979 www.exponent.com

EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies (2517-RGG)

Dear Mr. Gebken:

On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's), Exponent is providing a response to EPA's memorandum dated February 24, 2010 regarding efficacy and CASS Data Evaluation Records (DERs) for Sergeant's EtofenproxlNylar Spot-On Flea and Tick Products for Dogs and Puppies (EPA Reg. No. 2517-RGG). I will contact you in the near future to schedule a meeting with you and other Office ofPesticide Program's (OPP's) staffto discuss OPP's DERs and the Sergeant's response to the OPP reviews. Please find enclosed the following support documents:

• Transmittal document;

• EPA Form 8570-1;

• Enclosure 1. Sergeant's response to OPP's efficacy reviews for MRIDs 47849601, 47849602,47849603,47849604,47849605,47849606, and 47849607. The response provides a narrative discussion and tables ofdata consistent with that discussion;

• Enclosure 2. Revised Sergeant's Master Label for EPA Reg. No. 2517-RGG reflecting claims supported by the rebuttal discussion provided in Enclosure I;

• Enclosure 3. Sergeant's response to OPP's CASS review for MRID 47849609. The response provides a narrative discussion and tables ofdata consistent with that discussion, and also includes a response from the testing laboratory relative to a particular commentmade by OPP. 

### Included is

### Enclosure 3 Attachment A;

• Enclosure 4. Copy ofEPA efficacy review;

• Enclosure 5. Copy ofEPA CASS review; and

• Product-specific product chemistry data.Ifyou have any questions or need additional information, please contact me at 202-772-4932 or jmessina@exponent.com.

es Messina uthorized Representative of Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kevin Sweeney, EPA Kelly Hoskins, Sergeant's Larry Nouvel, Sergeant's Rick Tinsworth, ExponentData Transmittal Document:

Product: Sergeant's EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies 2517-RGG

Submitter: Sergeant's Pet Care Products, Inc. (EPA Company Number 2517) 2637 South 158th Plaza Suite 100 Omaha, NE 68130-1703

Return to: James Messina Exponent 1150 Connecticut Ave., NW Suite 1100 Washington, DC 20036

Submittal Date: April 9, 2010

Volume Study Title 1 Group A Product Chemistry for EtofenproxINylar SpotOn Flea and Tick for Dogs and Puppies (Alternate) 2 Group B Product Chemistry for EtofenproxINylar SpotOn Flea and Tick for Dogs and Puppies (Alternate) MRIDPlease read instructions on reverse before completing form Form Approved OMB No 2070 0060 Approval expi/es 05-3 t 98 

### . .
United States bJRegistration app Identitier Number 

# EPA Environmental Protection Agency D_Amendment Washington, DC 20460

### ~ Other
Application for Pesticide

- Section I
t. Company/Product Number 2, EPA Product Manager 3. Proposed Classification 2517·RGG R Gebken 4. Company/Product (Name) PM#

### ~None DRestricted Etofenprox/Nylar Spot-On Flea and Tick for Dogs and Puppies to (30%) 5, Name and Address of Applicant (/nclude ZIP Code) 6. Expedited Review. In accordance with FIFRA Section 3(c)(3)(b)(I), my Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to:
2625 South 158'h Plaza Omaha, NE 68130 EPA Reg. No. 69332·3

Product Name SPI #8208·55D

D Check ifthis rs a new address Section II 

# o Amendment

### ~ Explain below. 

# D Final printed labels in response to Agency letter dated

### XX~XX~XX

### ~ Resubmission in response to Agency letter dated

### 02~24~ 10 

# o "Me Toon Application 

# D Notification

- Explain below. 

# D Other

### ~ Explain below, Explanation: Use additional page(s) if necessary, (For section I and Section II.) Submission of a rebuttal to EPA memorandum dated 2124/10 and product-specific product chemistry data

Section III 1, Material This Product Will Be Packaged In:**Child~Resistant** Packaging Unit Packaging Water Soluble Packaging 2. Type of Container OVes' [gives Oves 

# o Metal ONo 

# o No fZj No 

### cg] Plastic If "Yes" No, per**If~Yes"** No, per DGlass 'Certification must Unit Packaging wgt Container Packagewgt. Container DPaper be submitted 2.0mL 

## I 1·6 

## I Dother (Specify) Plastic Bag 3. Location ot Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions fZjLabel 

# o Container 2.0mL Don Can Don Labeling accompanying product 6. Manner in Which Label is Affixed to product DUthograph DOther DPaper glued DStenciled Section IV 1. Contact Point (Comp/ele items directly below for idenfificalion ofindividual to be conlacled, ifnecessary, to process this appllcalion.) Name Title Telephone No. (include Area code) James Messina Authorized Representative (202) 772-4932 Certification S. Date Application I certify that the statements I have made on this form and all attachments thereto are true, accurate and complete, I Received acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both (Stamped) under aPR' e w,,......-, 2. Signatt

# il~ 3. Title BV: Authorized Representative

4. Typed Nampl' 5, Date: 

# 1-7-10 James Messina

### Enclosure 1
Response to February 12th, 2010, Decision 420097, 2517-RGG,**Re:~RlDs47849601,47849602,47849603,47849604,47849605,47849606,47849607** 

### EtofenproxlNylar Spot-on Flea & 

### Tick for Dogs and Puppies By: Thomas A.**~iIIer,** 

### B.Sc. (Agric),**B.V.~.S, D.V.~.,**  

### Ph. D.,**~.R.C.V.S,** 

### Consultant, VRRC Inc, Sequim, W A 98382Response to February 12th

, 2010, Decision 420097, 2517-RGG,**Re:~RIDs47849601,47849602,47849603,47849604,47849605,47849606,47849607** EtofenproxlNylar Spot-on Flea & Tick for Dogs and Puppies By: Thomas A.**~iller,** B.Sc. (Agric),**B.V.~.S, D.V.~.,**  Ph. D.,**~.R.C.V.S,** Consultant, VRRC Inc, Sequim, W A 98382

Rather than responding to individual comments on each study, the following re-analyses of the entire project data were conducted, based on the dose rates (mg/kg) of etofenprox delivered to all treated dogs. The dog weights entered in these analyses were limited to the label range of4 to 20 Ib, thus excluding MRID 47849601, since its weights exceeded the label range.

The label specifications (Table I) shows the dose rates, mglkg of etofenprox and pyriproxyfen applied in the 2.0 mL unit dose to dogs weighing from 4 to 20 Ib (1.8 to 9.1 kg). Since the claims in question are those related to the toxicant effect of etofenprox, the presence ofthe IGR, pyriproxyfen, will not be considered.

The dose rates of etofenprox (from a 55% squeeze-on) range from a maximum of 606 mg/kg for the smallest dog weighing 4 Ib to the minimum dose rate of 121 mg/kg for the heaviest dog weighing 20 lb. The mean +/- s. d. dose rates for the range are 252 +/- 138 mglkg.

The individual data for each treated dog in the efficacy study reports (MRIDs 47849603, 47849604, 47849606 and 47849607, excluding 47849605 that addresses only the Black Leg Tick, Ixodes scapularis) were entered showing dog weight (lb and kg), unit dose volume (mL) and etofenprox dose rate (mg/kg). The efficacy result for each treated dog (against re-infestation with new fleas and ticks, at or exceeding 90%, comparing each dog's flea and tick counts with the respective mean group flea and tick counts on the control group in that study) were extracted from the data tables (Table 2). Individual etofenprox dose rates ranged from 122 to 411 mg/kg, with mean +/- s.d. dose rates for these forty (40) treated dogs of 266 +/- 82 mglkg. Statistical analysis (by Student's "t" test, two-tailed, assuming equal variances, Microsoft Office 2003), comparing the range of label dose rates of etofenprox (252 +/- 138) with the values for these 40 treated dogs (266 +/- 82) showed that they were not significantly different (> 0.5), irrespective of the dose volumes applied to each treated dog. The post-treatment efficacy values against fleas and ticks ranged from 16 to 31 days with 3 outliers of 9 days (fleas only). The mean efficacy values (+/- s.d.) were 22 +/- 6.7 days for fleas and 25.4 +/- 4.7 days for ticks. Since the dose rates in the efficacy studies were not significantly different from the label dose rates at a 2.0 mL unit dose, these findings support at least a 3-week residual efficacy label claim for both fleas and ticks.

The data from Table 2 were copied into Table 3 and all results for treatments where the unit dose volumes exceeded the proposed label unit dose volume of2.0 mL were removed. This provided data on 18 treated dogs that received the proposed label unit dose volume or less (6 received only 1.5 mL). The mean +/- s.d. etofenprox dose rates for these 18 treated dogs were 214 +/- 89 mg/kg. These values were also not significantly different from the dose rates applied by the proposed label (P> 0.3). The mean +/- s.d. residual day's efficacy values for these 18 treated dogs were 20 +/- 6 days for fleas and 26 +/- 4 days for ticks. Again these results support an approximately 3 week claim for fleas and at least a 3 week claim for ticks.The minimum label dose rates for the heaviest label dogs (17-20 Ib) are under 150 mglkg (Table I). Extracting the data from 176D/47849606, provides mean residual efficacy of 17 days for fleas and 25 days for ticks for these 6 treated dogs that were at the upper limit ofthe label weight range. These data support at least a 2 week claim for fleas and more than 3 weeks for ticks.

The claims for efficacy against mosquitoes were partially rejected because the test dogs were limited by weight (163D 47849604) to small dogs. This is necessary because available Gerberg type mosquito cages are of limited sizes that necessitate the use of small dogs so that the anesthetized dogs can be totally contained in the cages and the free mosquitoes confined with the dog. This procedure and results reported in a previous efficacy study (MRID 47163701) have been accepted and label claims approved for registration numbers 2517-80,2517-85,2517-90. In the referenced report, mosquito tests were run on dogs under 201b. The data was considered adequate to enable registration of labels with no weight restriction, including dogs over 601b. The dogs were treated with 2.5 mL for a mean etofenprox dose rate of 364 mglkg approximating the middle ofthe range of label dose rates (121-606 mglkg). The "controls" mosquitoes claim is invalid and must be deleted but there is no "kills mosquitoes" claim on the proposed label. The mosquito data does however support a 30 day claim of repellency/preventing blood feeding by female mosquitoes

The Ixodes scapularis Black Leg Tick nymph test (163-2D 47849605) was conducted to the
same protocol that has been used previously and that secured registered labels with this claim ((MRID 46166109 2517-80, 85, 90). These labels were accepted with a 30 day claim even though the tests were conducted at 14 and 22 days after treatment. In 47849605, since the tests
were conducted only once, the proposed label does not associate any residual claim with this tick specie and the "long lasting" claim, has been removed. The suggestion that the test should have been run at 30 days becomes relevant only ifa 30 day claim would be on the proposed label.

The "quick acting" claim has been removed from the draft label since there were no flea or tick counts before 24 hours after treatment/re-infestation.

The pyriproxyfen IGR claims are supported by the results of a dose-titration study on dogs (MRID 46346601). That report supported registration of 2517-80. The label ofthat registration specifies a unit dose volume (at 2.2% pyriproxyfen) for dogs 20 lb and less of 1.5 

### mL. Although the etofenprox-Nylar label specifies unit dose volume of 2.0 mL, increasing the dose rate of pyriproxyfen by approximately one third, the label for 2517-RGG maintains the same approved residual IGR claims 2517-80.TABLE 1 Etofenprox-Containing Squeeze-On for Small Dogs Dosage and dose rates of active ingredients
Dog weight Active Etofenprox Pyriproxyfen Label potency**~,** 55.0% 2.2% Ib kg mL

## ~ mg/kg**~** mg/kg 4 1.8 2 

# I 606

### ~ 24 5 2.3 2 485 

# I 19 6 2.7 2 

## m 404 16 7 3.2 2 346 14 8 3.6 2 

# I 303

### ~ 12 9 4.1 2 269 11 10 4.5 2 243 10 11 5.0 2 220 9 12 5.4 2

## ~ 202 8 13 5.9 2 

# I 187 7 14 6.4 2 173 7 15 6.8 2 

# I 162 6 16 7.3 2 152 

## :. 6 17 7.7 2 ltl 143 6**~r** 

# I 18 8.2 2

# ~ 135 5 19 8.6 2 

### Hi 128 

# , 5 20 9.1 2

# ~ 121**~** 5 12 5 mean**~** 252 10**~** b 5 2 +/- s.d. 138 

# " 6**~** 

### ill Potency is label nominalTable 2 Etofenprox-Containing Squeeze-On for Small Dogs 

### Dosage and Residual Claim Support Dose rates mg/kg vs residual efficacy @ =/>90% All dogs weighing 4-20 Ib, irrespective of unit dose volumes applied Study no. MRID dog wt dose dose rate days @ =/>90% ka Ib mL mg/ka fleas ticks 149D 47849601 4.2 9.2 1.5 199 16 31 149D 47849601 5.5 12.2 1.5 150 16 23 149D 47849601 4.5 10.0 1.5 183 23 31 149D 47849601 4.8 10.6 1.5 173 16 31 149D 47849601 3.0 6.7 1.5 273 16 31 149D 47849601 2.0 4.5 1.5 407 16 22 154D 47849602 3.2 7.0 2 349 29 22 154D 47849602 4.4 9.8 2 249 29 22 154D 47849602 3.3 7.2 2 339 15 22 154D 47849602 4.4 9.8 2 249 29 29 154D 47849602 4.5 9.9 2 246 29 22 154D 47849602 4.0 8.8 2 277 15 29 154D 47849602 8.5 18.8 4 260 29 29 154D 47849602 9.1 20.0 4 244 29 29 154D 47849602 9.0 19.9 4 245 29 22 154D 47849602 7.1 15.6 4 313 29 29 154D 47849602 8.3 18.3 4 267 29 29 158D 47849603 3.8 8.3 2.5 367 23 23 158D 47849603 4.4 9.8 2.5 311 30 30 158D 47849603 4.5 9.9 2.5 307 30 30 158D 47849603 4.5 9.9 2.5 307 9 23 158D 47849603 3.7 8.2 2.5 371 16 30 158D 47849603 4.2 9.2 2.5 331 9 16 158D 47849603 9.4 20.8 4.7 274 23 23 158D 47849603 8.7 19.2 4.3 274 30 23 158D 47849603 9.4 20.8 4.7 274 30 30 158D 47849603 8.8 19.4 4.4 274 30 30 158D 47849603 8.7 19.1 4.3 274 23 30 158D 47849603 9.2 20.2 4.5 274 30 30 163D 47849604 3.6 8.0 2.5 380 23 16 163D 47849604 4.4 9.6 2.5 317 23 23 163D 47849604 4.5 9.9 2.5 307 23 16 163D 47849604 3.7 8.1 2.5 376 23 23 163D 47849604 4.5 10.0 2.5 304 23 16 163D 47849604 3.4 7.4 2.5 411 23 23 176D 47849606 8.3 18.3 2.0 133 9 23 176D 47849606 8.4 18.6 2.0 131 15 23 176D 47849606 8.6 19.0 2.0 128 23 30 176D 47849606 8.9 19.6 2.0 124 16 30 176D 47849606 9.0 19.9 2.0 122 23 23 176D 47849606 9.1 20.0 2.0 122 16 23
mean 6.0 13.2 2.7 266.2 22.4 25.4 +/- s.d. 2.4 5.4 1.0 82.1 6.7 4.7 PACE study excluded since all dogs were well over 20 Ib 

# EX'Table 

### 3 Etofenprox-Containing Squeeze-On for Small Dogs =/< 2 mL dose to dogs 4-20 Ib
Study no.lMRIO dogwt kg dose dose rate days @ =/>90% kfl Ib mL mfl/kfl fleas ticks 1760 47849606 9.0 19.9 2.0 122 23 23 1760 47849606 9.1 20.0 2.0 122 16 23 1760 47849606 8.9 19.6 2.0 124 16 30 1760 47849606 8.6 19.0 2.0 128 23 30 1760 47849606 8.4 18.6 2.0 131 15 23 1760 47849606 8.3 18.3 2.0 133 9 23 1490 47849601 5.5 12.2 1.5 150 16 23 1490 47849601 4.8 10.6 1.5 173 16 31 1490 47849601 4.5 10.0 1.5 183 23 31 1490 47849601 4.2 9.2 1.5 199 16 31 1540 47849602 4.5 9.9 2.0 246 29 22 1540 47849602 4.4 9.8 2.0 249 29 22 1540 47849602 4.4 9.8 2.0 249 29 29 1490 47849601 3.0 6.7 1.5 273 16 31 1540 47849602 4.0 8.8 2.0 277 15 29 1540 47849602 3.3 7.2 2.0 339 15 22 1540 47849602 3.2 7.0 2.0 349 29 22 1490 47849601 2.0 4.5 1.5 407 16 22

mean 5.6 12.3 1.8 214 20 26 +/- s.d. 2.4 5.3 0.2 89 6 4

### EncIosure2

Revised Product Label

# Sergeant's Pet Care Products, Inc. Master Label

10 September 2009 EPA Reg. No. 2517-XX Infonnation in [ ] is optional. Page I of4 EPA SAL

Editors Note: [Optional proposed text appears in brackets

- the final label may
ETOFENPROXINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES
{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On} {ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small breed dogs} {ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small and toy breed dogs} {ABN: Sergeant's Small Breed Flea and Tick Squeeze-On} {ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small breed dogs} {ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for dogs} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for Dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small breed dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small and toy breed dogs}
[One Application:(choose from the following)]

• [with nylar®]

• [(One) (Two) (Three) (Four) (XX) Applications]

• [Bonus] 33% more [now includes 4 tubes]

• [odorless] [unscented] [fragrance free]

• [Dries quickly] [Quick drying fonnula] [Quick Drying]

• [Squeeze-On] [stays on and doesn't rub off]

• [Spreads by using the dog's natural skin oils]

• [Breaks the flea life cycle for up to (70 Days) (9 Weeks)]

• [Controls reinfestation for up to (70 days) (9 weeks)]

• [For toy breeds 4-20 Ibs.]

• [For small breeds 4-20 Ibs.]

• [For toy and small breeds 4-20 Ibs.]

• [Specially fonnulated for small breed[s] dogs]

• [Specially fonnulated for toy breeq[s] [dogs]]

• [Specially fonnulated for [toy breed[s]] and [small breed[s]] dogs]

• [Toy] [and] [small] breed fonnula]

• [Gentle protection for [toy] [small] breed dogs]

• [5 Way Protection]

• [Controls fleas, ticks, flea eggs & larvae]

• [Kills Fleas, Ticks, Flea Eggs, Larvae] [and] [repels mosquitoes [for up to one month] [for up to 4 weeks]]

• [Flea, tick, flea egg and larvae control]

• [Kills fleas and ticks for up to [21 days] [3 weeks]]

• [Kills ticks [for up to [21 days] [3 weeks]]]

• [Kills Ticks] [Before they can] [that] [transmit Lyme Disease

• [Kills [adult] fleas for up to [21 days] [3 weeks]]

• [Kills Fleas and Ticks] [for up to [21 days][3 weeks]]

• [Flea, Tick and Flea Egg Protection]

• [Repels mosquitoes [for up to one month] [for up to 4 weeks]]

• [Flea and Tick control]

• [Kills fleas that may cause flea allergy dennatitis, and flea bite anemia] [for up to [21 days] [3 weeks]]

• [Kills Flea Eggs and Larvae for up to (9 weeks) (70 days) (per application)]

• [Prevents flea eggs from developing into biting adults for up to (9 weeks) (70 days) (per application)]

• [Repels mosquitoes that may transmit [heartwonn] [West Nile virus] [from feeding on dogs] [for up to [one month] [30 days][ 4 weeks]]

# Sergeant's Pet Care Products, Inc. Master Label
10 September 2009 EPA Reg. No. 2517-XX Information in [ jis optional. Page 2 of4 EPA SAL

• [Repels Mosquitoes] [Prevents mosquitoes that transmit West Nile virus and heartworm] [from feeding on dogs] [for up to [one month] [30 days] [ 4 weeks]] 

## •**:mB~~~~~~~~5'"""fi;'~'**

ACTIVE INGREDIENTS: Etofenprox

..................................................................................... 55.00% Pyriproxyfen...................

................. ........... ............................ ....... 2.20% OTHER INGREDIENTS:

....................................................................... 42.80% TOTAL 100.00%
[Nylar® is a registered trademark ofMcLaughlin Gormley King Company]



### KEEP OUT OF REACH OF CHILDREN 

### CAUTION See [Back][or][Side] Label Panel[s] for Additional Precautionary Statements

NET CONTENTS: [One] [Two][Three][Four][Five][Six] 2.0 mL applicators.lfor small dogs 4 to 20 lbs/

# Sergeant's Pet Care Products, Inc. Master Label
10 September 2009 EPA Reg. No. 25 I7-XX Information in [ J is optional. Page 3 of4 EPA SAL



## {Product Name}
READ ENTIRE LABEL BEFORE EACH USE

PRECAUTIONARY STATEMENTS HAZARDS TO HUMANS AND DOMESTIC ANIMALS 

### CAUTION

HAZARDS TO HUMANS: Causes moderate eye irritation. Avoid contact with eyes and clothing. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, or using tobacco.

HAZARDS TO DOMESTIC ANIMALS: For External Use Only. Do not use on dogs under 12 weeks of age. Consult a veterinarian before using this product on debilitated, aged, medicated, pregnant, or nursing animals. Sensitivities may occur after using ANY pesticide product for pets. Ifsigns of sensitivity occur, bathe your pet with mild soap and rinse with large amounts ofwater. Ifsigns continue, consult a veterinarian immediately.

FmST AID IF IN EYES: Hold eye open and rinse slowly and gently with water for 15-20 minutes. Remove contact lenses, if present, after the fITst 5 minutes, and then continue rinsing. Call apoison control center or doctor for treatment advice. Have the product container or label with you when calling a poison control center or doctor or going for treatment. You may also contact 1-800-781-4738 for emergency medical treatment information.

PHYSICAL OR CHEMICAL HAZARDS: Combustible: Do not use or store near heat or open flame.

DIRECTIONS FOR USE It is a violation ofFederal Law to use this product in a manner inconsistent with its labeling.

Do not get this product in your pet's eyes or mouth. Do not apply more often than [once a month] [once evel)' 30 days]. Use only on Dogs. FOR EXTERNAL USE ON DOGS ONLY. Do not use on puppies less than 12 weeks ofage. Weigh your dog to be sure you are applying the right dose formulated for the weight ofyour pet. Do not treat your pet with more than one pesticide product at a time. Over dosing your animal can result in serious illness and even death. Best ifused year round. Do not bathe pet with in the first 24 hours after squeeze-on has been applied. Households with more than one pet should not allow dogs or cats to groom each other until solution has dried. DO NOT USE ON CATS or animals other than dogs. Separate the treated dog from all other dogs and cats for 24 hours after treatment has been applied. Cats or dogs that actively groom or engage in close physical contact with treated dogs may be at risk of serious harmful effects. Ifyour dog is exhibiting signs ofand/or are being treated for skin dermatitis, talk to your vet before applying any topical flea and tick control product. Sensitivities may occur after using ANY pesticide product on pets. It is recommended to separate treated dogs from other household pets for 24 hours after treatment has been applied. If signs ofsensitivity occur, bathe your dog with mild soap and rinse with large amounts ofwater.

FOR USE ON DOGS: Weighing 4 TO 20 LBS.

- Apply contents ofone (2.0 mL) tube [vial] of [Product Name][Squeeze-on] as a spot high on the back ofthe dog's neck behind its head and apply as a stripe to a point midway between the neck and the tail. (INSERT DIAGRAM THAT DEPICTS APPLICATION OF PRODUCT ON THE DOG)

HOW TOAPPLY: Remove product tube [vial] from the package. Holding tube [vial] with notched end pointing up and away from the face and body cut or tear offthe narrow end at the notches. While holding the animal with one hand, use the other hand to apply the solution. Invert the tube [vial] and use the narrow end to part the animal's hair while gently squeezing to apply to the animal's skin. Hold the animal for a few seconds to give the solution time to be absorbed into the animal's coat. When fInished, wrap the tube [vial] in paper and put into the trash.

# Sergeant's Pet Care Products, Inc. Master Label
10 September 2009 EPA Reg. No. 2517-XX Information in [ J is optional. Page 4 of4 EPA SAL

STORAGE AND DISPOSAL Do not contaminate water, food or feed by storage or disposal. PESTICIDE STORAGE: Do not remove tube from the pack until ready to use. Store in a cool (below 25'C) dry place out ofreach ofchildren. Do not refrigerate. Protect from direct sunlight.

PESTICIDE DISPOSAL: Nonrefillable container. Do not reuse or refill this container. Offer for recycling or reconditioning, ifavailable and appropriate. Ifempty: Do not reuse this container. Place in trash or offer for recycling ifavailable. Ifpartly filled: Call your local solid waste agency for disposal instructions. Never place unused product down any indoor or outdoor drain.

[WARRANTY Read the entire Directions for Use and Warranty before using this Product. By using this product, user or buyer accepts the following warranty. [[The directions for use ofthis product are believed to be adequate and must be followed carefully. However, it is impossible to eliminate all risks inherently associated with the use ofthis product. Unintended consequences may result because ofsuch factors as weather conditions, presence or absence ofother materials, or the manner ofapplication, all ofwhich are beyond the control ofSergeant's Pet Care Products, Inc

..JJ Sergeant's Pet Care Products, Inc. is committed to providing high quality products. To the extent consistent with applicable law, Sergeant's Pet Care Products, Inc. makes no warranties, express or implied, ofmerchantability or of fitness for a particular purpose or otherwise, that extend beyond statements on this label. To the extent consistent with applicable Jaw, Sergeant's Pet Care Products, Inc., the manufacturer, or the Seller disclaims any liability whatsoever for special, incidental, or consequential damages resulting from the use ofthis product. To the extent consistent with the law, the exclusive remedy ofthe user or buyer shall not exceed the purchase price paid.J
[Sergeant's Care Pet Products, Inc. is committed to providing high quality products. Ifyou have questions or comments about this product, please write: Sergeant's Consumer Response, P.O. Box 540399, Omaha, NE 68154- 0399.J

In Case ofEmergency, call: 1-800-781-4738 Non-Emergency call: 1-800-224-PETS (7387)

Distributed by:
Sergeant's Pet Care Products, Inc. PO Box 540224 Omaha, NE 68154 {END

- BACK I SIDE PANEL)

### ~~jAY~~lm Front Label {Product Name) Etofenprox

..........55.0% WIW Pyriproxyfen

.........2.2% WIW 2.0mL {Jabel code} [For more information] [Visit us at:] www.sergeants.com Made in USA

EPA Reg. No. 2517-XX EPA Est. No. XXXXXXX {date & label code)



### BackLabel

KEEP OUT OF REACH OF CHILDREN CAUTION: Read directions and precautions before using. EPA REG. No. 2517-XX {label code)

### Enclosnre 3
Response to February 24'h, 2010, Decision 420097, 2517-RGG, Re: MRID 47849609 EtofenproxINylar Spot-on Flea & 

### Tick for Dogs and Puppies By: 

### Thomas A. Miller, B.Sc. (Agric), B.V.M.S, D.V.M., Ph. D., M.R.C.V.S, Consultant, VRRC Inc, Sequim, W A 98382Response to February 24th

, 2010, Decision 420097, 2517-RGG, Re: 

### MRID 47849609 EtofenproxlNylar Spot-on Flea & Tick for Dogs and Puppies By: Thomas A. Miller, B.Sc. (Agric), B.V.M.S, D.V.M., Ph. D., M.R.C.V.S, Consultant, VRRC Inc, Sequim, W A 98382

1. Reviewer's comment: "Test groups consisted of6 (3 male and 3 female) adult dogs or puppies".
Response: The 5Xdosage rate test group consisted of 6 puppies (3 male and 3 female) and 6 adult dogs (3 male and 3 female), total 12 animals (6 males and 6 females) in this dose rate test group. This conforms to the 870-7200 Guidelines.

This protocol and dose grouping are essentially the same as the protocols and grouping in previous CASS reports (MRlDs, 46161309 & 46166108) that were accepted and supported several registrations including the following: 69332-3 & 2517-80. All were based on the referenced 1998 Guidelines which have not been amended since issue. That the IX test group consisted of only 6 adults (3 males and 3 females) becomes irrelevant if there are adequate safety-supporting data from the 5X group. The presence of a IX dose rate test group in the referenced CASS guidelines represents a fall-back "rescue" position should there be adverse effects at 5X.

2. Reviewer's comments: "In addition, the adult dogs that were treated with the test substance II (containing

.......) at 5X the dosage rate weighed

......... Since only one dog in this group weighed less than 9 Ib, the data could not be used to support

.... "
Response: The separation of the adult from the puppy 5X subgroups, rejected above, is artificial. The primary concern in CASS evaluation is that puppies are more likely to be susceptible to adverse effects of pesticides and that, depending on dose rate (mg a.i. per kg body weight), they should be more vulnerable, otherwise, there is no rationale for requiring separate testing of pups from adults. The IX and 5X puppy subgroups contained pups weights ranging from 4.71b up to 16.11b, spanning most ofthe proposed label range of4 to 20 lb. The 5X adult subgroup contained dogs weighing from 9 to 20 !lb. The entire label weight range for puppies and small dogs was therefore adequately covered.

3. Reviewer's comments: "Cumulative dosage rates were

........, which is also substantially above the proposed lower weight limit"
Response: These statements do not accurately portray the dosages/dose rates ofactives applied to the CASS test subjects. Table I calculates the dose rates (mg/kg) of each active ingredient that was applied to each test dog (with group mean dose rates +/- S.D.) in this study. Table 2 shows the label

### dose rates of etofenprox and pyriproxyfen (at upper certified limits of the CSF) administered to dogs and puppies from 4 to 20 lb. For the purpose of my response I will only address the etofenprox component since that would be the primary culprit in inducing any adverse effects. The other component of the product (pyriproxyfen insect growth regulator) is virtually mammalian-inert. The mean group CASS dose rates for the active at I X and 5 X, for dogs (5X CASS rate) and puppies (lX and 5X rate) are copied from Table I and entered at the top of the columns that calculate and display the ratio between CASS dose rates and label dose rates. The ratios never exceed and only approach a single dose value of I (i.e., 0.92) for the smallest (4Ib) dogs/puppies specified on the proposed label. The ratio, based on the 5X CASS puppy dose rate, is approximately 17% of the 5X CASS dose rate. At the upper weight limit of 20 Ib, the dogs receive approximately one third ofthe IX puppy dose rate, 14% ofthe IX CASS adult dose rate and only 7% ofthe 5X CASS puppy rate. The reviewer's calculations become irrelevant in comparison with these data.

4. Reviewer's comments: "Also 

### it was not possible to compare body weight changes between adult group B3 and the control (C2) group because initial

........."
Response: When considering weight changes after treatment, "adult dogs are adult dogs", irrespective of differences in body weights. Because ofthe need to address weight changes over the wide span of adult dogs' weights that represent the dog population and the label weight range, instead of analyzing weight changes based on individual weights before, after and gains therein, percent weight changes for each animal provide a more appropriate method. The individual weights on days 1,7 and 14, extracted from the [mal report, were transformed to provide (Table 3) changes
over the test periods of 1-7, 7-14 and 1-14 days after treatment, then to change per day and [mally to % (of weight at start of each interval) per day. Student's "T" test was used to determine the significance of apparent differences in % change per day between groups pups B3 and C2 (groups that received etofenprox only (over each of these three periods). There were statistically significant differences for days 1-7 and 1-14, in that the daily weight % changes/gains ofthe treated dogs were lower (P<0.05), but not between days 7 and 14. However,
as noted the weight ranges of the treated dogs and the controls did not coincide. It 

### is not clear whether the different ranges were responsible for the significant differences or whether it was application of the etofenprox test substance. However, the same data transformations and analyses, applied to the puppies that received, in addition to the etofenprox, cyphenothrin, fipronyl and two IGRs (Table 4) showed no evidence oftreatment-mediated changes in % daily weight changes (gains) for treated compared with placebo-treated control puppies over any ofthe three test intervals. Since puppies are assumed to be more vulnerable to adverse effects of insecticide treatment compared with adult dogs and since these treated puppies also received two additional insecticide actives and an additional IGR, it is clear that the significant differences in the adult data were a function of the different and non-overlapping weight ranges and not an indication oftoxicity.

### 5. Reviewer's comments: "For the puppies, it is impossible to compare and interpret differences in body weight gains when there was such a range in ages (10-15 weeks with no information as to specific ages for individual animals), the dogs were mixed breed and

..........control group"
Response: The records for puppy birth date, date oftreatment and individual weights at treatment and days 7 and 14 were obtained from the investigator. Age at treatment (days) were calculated (Table 5). Ages on day of treatment ranged from 73 days (10 weeks) to 106 days (15 weeks), with mean group ages of 12.5 weeks (group AI), 13.1 weeks (group A2) and 14.1 weeks (group CI). There
were no significant differences between these groups' ages (P> 0.05).

The group weights at time oftreatment were analyzed (Table 5) and found not to be significantly different (P>0.05). Weigh gains over the duration ofthe study were shown not to be statistically different (paragraph 4 and Table 5).

The proposed labels read "for dogs and puppies 12 weeks and older". While it may be argued that more uniform groups ofpups might have been used with a tighter age and weight range, this is achievable only with purpose-bred pups, invariably Beagles, not with mixed breeds for which the product will be labeled.

For many safety/toxicology studies, the exclusive dependence on closed colony Beagles has been questioned as not always providing results that can be uncritically applied to the general pet population. Availability of sufficient mixed breed pups with a tight age distribution at a specific start 

### date necessitates a very large pool of simultaneously bred bitches, a requirement that is unrealistic (except for Beagles maintained under controlled, programmed climatic/seasonal light and temperature environments).

6. Reviewer's comments: "In addition, it is concluded that the margin of safety in puppies administered

...substances IA and II.

..was less than the I X recommended dose

......"
Response: Table 2, discussed in paragraph 3 (above), clearly shows that for etofenprox and pyriproxyfen, administered at IX dosage to the safety study dogs and puppies, the ratio of label dose rate (mg/kg) to dose rates administered to the test dogs and puppies was less than I for dogs weighing 4 to 201b, as listed on the proposed label. Further this safety margin or ratio, based on the 5X dose rate test dogs and puppies, was from 0.06 to 0.17.7. Reviewer's comments: 

### "In addition, it is concluded that the margin of safety in puppies

......based on clinical signs of toxicity (behavioral change immediately post-application" and "showed running and circling

.......after application

........area had been numbed"
Response: 

### The investigator was asked to provide more information on these observations and questioned on whether he considered that the immediate post-application behavioral effect was a sign of local irritation from the topical application ofthe test substances. His response (attachment A), and I believe that of any veterinarian experienced in the often abnormal behavior of institutionalized experimental dogs, was that such behavior is common when one restrains and handles laboratory experimental dogs and applies any wet or cold substance to the back. They try to run away but since they are in a cage they can only move in a circular motion due to the physical constraints of the cage. This fleeing from the handler was very brief (one or two turns), was not accompanied by any vocalization, scratching of, or attempt to lick, the application area. The investigator (see appendix report from Clinvet) considers this behavior not to be evidence of toxicity or an adverse effect. The fact that the sequential 4 applications to the 5X dogs and puppies did not induce this "escape" behavior indicates that the dogs quickly accommodated to the application since they did not perceive the procedure ofre-applying the test substances as irritating, itchy or painful and there was no evidence of subsequent dermal pathologic change. The proposal by the reviewer that the test substances had any analgesic or topical anesthetic properties that "numbed" the area is unsupported and presumptious conjecture.

A previous CASS on dogs and puppies (MRID 46166208) for a test substance containing five times the present level ofcyphenothrin (40% 

### + lOR) caused some adverse effects, but only at 5X dosage level. Ocular discharge and some salivation were recorded but no neurologic effects. However this study was conducted by a different institution (in the US) and the "fugitive" behavior was not seen. Another CASS (MRID 45121109, conducted by the same US facility) of

an etofenprox spot-on (55%+ lOR) applied to cats and kittens induced no adverse effects. Felines are recognized as being much more sensitive to pesticides and 

### more likely to show adverse effects, especially of a neurological nature, than dogs. These previous CASS results support the registrant's contention that the very brief episodes of running and circling seen immediately after test substance application in the present CASS are not evidence of adverse effects but similar to the following observations.

Veterinarians and their staff are well aware of the conditioned reflex shown by pets that have previously visited the clinic. Most pets will not enter the building without being leashed or caged. The "fugitive or flight" behavior of some of the test dogs after first test substance application is very likely a conditioned reflex learned from previous treatment and handling experiences.

8. Reviewer's Comment: 

### "The application sites ofall dogs in Group B3 (5X application oftest substance II) had an oily or wet appearance

....Persistence oftest substance II on the hair ofdogs for more than 14 days is of
concern due to potential human exposure ofowners to pets."Response: 

### The oily or wet appearance involving a 5X application is not indicative ofthe appearance ofthe product as it is sold and used. EPA has conducted risk assessments and determined that the intended exposure for each ofthe active ingredients in test substance II is acceptable in currently registered products.TABLE1(page1)DosageChartforSergeanfsProposedFipronyl-ContainingSqueeze-OnsLabelsforDogsDosageratesdeliveredintheCASSDogTestDoseFironIIAChenothrinIANlarIIMethoreneIINlarIII)MethoreneIIIEtofenrox(II10GroupNoWeightsubmL8.808',2.318.82.4308.90°055°0lasedosesIbkSsinalemslksmslksmslkgmslkgmglkgmslkgmglkg8A81DA81Iadutt142.719.381A&11I1.346.085.671.686.1598510581Iadult138.417.441A&1I11.346.766.301.876.64CD530881Iadult134.915.821A&III1.347.456.952.067.544352FE81Iadult137.016.801A&1I11.347.026.541.947.1043680181Iadult134.515.661A&III1.347.537.022.087.6298500081Iadult124.911.301A&III1.3410.449:722.8810.55Mean35.416.17.57.02.17.6+/-S.D.5.9 2.71.51.40.41.5CD358582Iadult542.019.041A&III1.3430.9728.868.5531.329AF03882Iadult538.817.621A&11I1.3433.4631.189.2433.8489CD3382Iadult533.415.141A&III1.3438.9436.2910.7539.398A908682Iadult535.416.041A&III1.3436.7634.2510.1537.1896361882Iadutt535.316.021A&III1.3436.80 34.2910.1637.22CD4EAE82Iadult520.99.501A&11I1.3462.0657.8317.1462.77Mean34.315.61.339.837.111.040.3+1-S.D.7.23.30.011.2 10.53.111.498577283Iadult519.48.78II4.50225.001413.5598386083Iadult517.67.98II4.50247.561555.269598D683Iadult515.47.00II4.50282.211773.0088613883Iadun520.19.10II4.50217.091363.8568F15783Iadult519.78.94II4.50220.971388.268A991783Iadult59.04.06II4.50486.583056.90Mean16.97.6279.91758.5+1-S.D.4.21.9104.1654.16CC3A1C2142.819.40IVA1.0095682DC2137.216.88IVA1.00965249C2136.616.60IVA1.009AF246C2137.917.18IVA1.00984C4DC2129.213.26IVA1.0089D6C2C2128.713.00IVA1.00Mean35.416.1+1-S.D.5.52.5CV0855,TABLE1(page2)DosageratesdeliveredintheCASSDog-TestDoseFipronyl(IA)cyphenothrin(IA)Nlar(II)Methoprene(II)Nlar(III)Mathorene(III)Etofenprox(II)10GroupNoWeightsubml8,8%82,31%8.78%2.43c/c8.90%55%IagedosesIbkasinglema/karna/kgma/kamglkgma/kamglkamglkgCD5C9CAllpup12.15.48IA2,0032.1229.9312.15.48II7,5031.61120.16754.93COBF23AlIpup111.45.16IA1.8331.2129,08111.45.16II6.9030.89117.41737.60CC647BAllpup14.72,14IA0.8334,1331.8014.72.14II3.1033.46127,19799.05CD6lA8AlIpup112.35,56IA2,0031.6529,50112.35.56II7.5031.16118.44744,06CD4FE6Allpup111.04.98IA1.8332,34 30,13111.04.98II6.9032,01121.65764.27CD62COAllpup14,72,12IA0.8334.45 32.1014.72.12II1,3014.1753.84338,25Mean9.34,232.730.428.9109.8689.7+1-S.D.3.61.61,31.27.327,6173.5CDCECAA2Ipup516,17.32IA2.66159.89 148.99516,17,32II10.00157.79599.733767,76CD4407A21pup59.34.20IA1.50157.14146.4359.34,20II5.62154.55587,423690.47CD656CA2Ipup56.02.70IA1.00162.96151.8556.02.70II3.76160,64611.353640.77CD6OAEA2Ipup515,36.96IA2,50158,05147.27515.36.96II9,38155.66591.643716.96CD5A8DA2Ipup510.84,88IA1,84165.90154.59510,84,88II6,88162.84618.923888.33CD5OFBA21pup57.83.56IA1.34165,62154.3357.83.56II5.00162.22616.573873.60Mean10,94.9161.6160.6159.0604.33796.3+1-5.0.4.11.93,83.5 3.513.383.3CC7692Cllpup521.39.67IVA2.62CD3lAECllpup56.62.98IVA0.88CD44BCClIpup56.32.88IVA0.74CD47ECCllpup517.17,76IVA2.12CC6224Cllpup59,94.50IVA1.24CD4A2BCl/pup58.03.62IVA1.00Mean11.55.2+1-5,0,6.22,8CV0855,,TABLE2DosageChartforSergeant'sProposedEtofenprox-ContalnlngSqueeze-OnLabelforSmallDogsJustificationExtrapolationfromCASSCV0855DogweightActiveEtofenproxCASSdosePyriproxyfenCASSdoseLabelpotency55.0%ratefactor2.2%ratefactor@UCLofCSF57.8%1X5X2.3%1Xpuppies689.73796.328.9adults1759.02.1IbkgmLmQlkgmQlkQ41.82636.60.920.1725.50.8852.32509.30.740.13120.40.7162.72424.40.620.1117.00.5973.22363.80.530.1014.60.5083.62318.30.46 0.0812.70.4494.12282.90.410.1611.30.39104.54509.30.740.2920.40.71115.04463.00.670.2618.50.64125.44424.40.620.2417.00.59135.94391.70.570.2215.70.54146.44363.80.530.2114.60.50156.840",339.50.490.1913.60.47!!:J•.167.34J318.30.460.18!12.70.44177.74299.60.430.1712.00.41188.24282.90.410.1611.30.39198.64268.00.390.1510.70.3720914254.60.370.1410.20.35---_.PotencyisuppercertifiedlimitonConfidentialStatementsofFormulaeItalicisedCASSfactorbasedonmeangroupdoseratestothesmallestdogstested(12-15weekoldpuppiesl,allothersbasedonadultCASSmeangroupdoserates5X159.011.00.160.130.110.090.080.070.130.120.110.100.090.090.080.080.070.070.06Table3%dailyweightchanges aftertreatmentdateforadultsreceivingetofenproxandpyriproxyfenBodyWeights.kgdiange/dax%Changefday''?"valuedays17141-71-141-77-141-141-71-141·71-1417141-77-141-141-77-141-141-77·141-14838.78.448.56-0.260.12·0.14-0.037140.017143-0.01000·0.427%0.203%-0.00115P<0.05>0.3<0.058.188.3-0.10.30.2-0.014290.0428570.01429·0.176%0.536%0.001764C26.7876.940.22-0.060.160.031429-0.008570.011430.464%·0.122%0.0016869.089.149.020.06-0.12-0.060.008571-0.01714-0.004290.094%-0.188%-0.000479.069.169.080.1-0.080.020.014286-0.011430.001430.158%-0.125%0.000158833.983.96 3.98-0.020.020-0.002860.0028570.00000-0.072%0.072%0Mean1.627.62 7.650.000.03 0.030.0000.0040.0020.007%0.063%0.033%17141-77-141·141-77·141-141-77-141-1419.419.6619.620.26·0.040.220.037143-0.005710.015710.191%-0.029%0.0008117.0617.4217.280.36-0.140.220.051429-0.020.015710.301%-0.115%0.00092116.7617.717.940.94 0.241.180.134286 0.0342860.084290.B01%0.194%0.00502917.4618.2617.70.8-0.560.240.114286-0.080.017140.655%-0.438%0.00098213.7214.514.320.78-0.180.60.111429-0.025710.042860.812%-0.177%0.003124C213.414.0214.160.620.140.760.0885710.020.054290.661%0.143%0.004051Mean16.3016.93 16.840.63-0.090.640.090-0.0130.0380.570%..0.070%0.249%Conclusions:1group83(etofenproxadults5X)showedsmallerdailypercen1weigh1changes(gains).comparedwiththeuntreatedcontrols2therewerenosignlfican1differencesinweigh1gainsIntreatedadultsbetween1Xand5Xdoserates(group81VS82)t],Table4%dailyweightchangesaftertreatmentdateforpuppiesthatreceivedetofenprox,cyphenothrin,fipronyland1heIGRsBodyWeights.kgchangechange/day"P"valueday17141-77-141-141-77-141-141-77-141-141-77-141-14Al5.365.9B6.660.620.6B1.300.090.100.Q91.65%1.62%1.73%4.925.726.5BO.B0.B61.660.110.120.122.32%2.15% 2.41%Al22.22.240.20.040.24 0.030.010.021.43%0.26%0.86%P>0.1>0.5>0.75.96.547.460.640.921.560.090.130.111.55%2.01%1.89%C!5.545.B66.B0.320.941.260.050.130.090.83%2.29%1.62%2.062.3B2.BB0.320.500.B20.050.070.062.22%3.00%2.84%mean4.34.85.40.48 0.661.140.070.09O.OB1.7%1.9%1.9%A27.64B.128.54O.4B0.420.900.070.060.060.90%0.74% 0.84%A24.24.745.520.540.7B1.320.080.110.091.84%2.35%2.24%P>0.3>0.3>0.82.73.02 3.340.32 0.320.640.050.050.051.69%1.51%1.69%Cl7.267.76BAB0.50.721.220.070.100.090.98%1.33%1.20%4.965.76.620.740.921.660.110.13 0.122.13%2.31%2.39%3.5B3.924.40.34 0.480.820.050.070.061.36%1.75%1.64%Mean5.15.56.20.490.611.090.070.090.081.5%1.7%1.7%Cl10.4611.4211.860.960.44lAO0.140.060.101.31%0.55%0.96%Al3.143.544.240.40.701.100.06 0.10 0.081.82%2.82%2.50%P>0.5>0.6>0.52.B63.13.540.240.440.680.030.060.051.20%2.03%1.70%A27.747.788.880.041.101.140.010.16O.OB0.07%2.02%1.05%4.B65.446.10.58 0.661.24O.OB0.090.091.70%1.73%1.82%3.924.085.320.161.241.400.020.180.100.58%4.34%2.55%Mean5.55.96.7 0.40 0.761.160.060.110.081.1%2.2%1.8%Conclusions:11herewerenosignificantdifferencesindailypercentweightgainsbetweentreatedandcontrolpupsorbetweenthe2groups(1Xvs5X)oftreatedpups.2treatment.evenat5Xhadnoadverseeffectonthegrowthofthesepuppies,Table5Analysisofpuppyweightsandagesattreatmentgroupdosageagesweights@treatmentweeksdifference"I'Testalleskll"r'TestweillhtA2591A15.48A1A2587"0.055.16"0.4A2579C12.14C1A251065.56A25734.98A25872.12mean87.212.5 12.54.2+/-s.d.11.31.61.61.6A1194A27.32A2A1187"0.14.20"0.8A1179C12.70C1A11996.96A11994.88A11913.56mean91.513.113.14.9+/-S.d.7.71.11.11.9C1control106A19.67A1C1control91"0.42.98"0.5C1control91A22.88A2C1control1067.76C1control994.50C1control993.62mean98.714.114.15.2+/-S.d.6.71.0 1.02.8eV0855,

### Enclosure 3 Attachment A

Letter from ClinVetSANAS SANAS

# ~c!P (.QUlltUNICllPR.\C/or./ IOOGG**lAU~.IOn. ~n~o!lCI** 

II March 2010
Sergeant's Pet Care products PO Box 261248, Plano, Texas, 75026 United States of America

Dear Dr Miller INTE:RNATIONAL IPTYj LTD

For attention: Dr Thoma') Miller

FINAL REPORT: STUDY CV 08 55l PERFORMIlD AT CLINVIlT

I refer to your comments on the recorded signs in some ofthe dogs after topical application ofthe test item.

Areas that were shaved

The application sites were not shaved. We did clip/shave (using an electric clipper) the areas of blood collection over the jugular vein.' Some dogs are more sensitive than others and a rash sometimes OCCur
011 such a clipped area. This skin condition was noted (and specifically mentioned to be present during application) to ensure that it was not considered a reaction to the test item during post application observations.

2 Running in circles:

Two ofsix puppies in group A I and four of six in group A2 did some running in circles immediately after application. It lasted one or twO circles in the pen and then they calmed down. No scratching or attempts at licking. No vocalisation.
Our**impr~ssion** was that the puppies were stimulated by the application ofa liquid. They got used 10 the effect ofbeing wet and no similar signs were seen after the following applications. 1 doubt very much if any owner will regard this behaviour as abnonnal or irritating.

.

Note: We observe all kinds of changes in behaviour after topical application oftest items in studies. The

mere presence ofa wet compollnd is llsually enough to make the animal run away. Only in this case there were boundaries (pen walls) and it could only run in circles. The question that needs answering is "WllY only the test item groups"? and why the behaviour change and no other s'tgns of irritation on the skin. A subjective conclusion was that the test items may have been cold (or felt cold, maybe as result ofevaporation?). That could be the reason why the pups did not react after the next appl icanons and also why no signs were seen on the skin and why no other changes were recorded. The important issue is that animals react differently to wet applications and in the one group the dose volume was 5 times higher than recommended. lfno clinical signs are observed 1 behaviollral changes cannot necessarily be seen to be as reSllh of an irritant.

Yours

### falthf~c: 

# J/-

Dr P el port (BVSCZ: director ClinVet International (Pty) Ltd Dr PC Oe/port B V Sc SAVe reg no D 70 10903 Veterinarian

.,1" jj" ".". '.1,;·.. "; "

### Enclosure 4
Copy ofEPA Efficacy Review

### Efficacy Review

Date: February 12, 2010 Efficacy Reviewer: Clayton Myers, Ph.D., Entomologis tll'ers.ela'ton,a; 703-347-8874

Risk Manager Rev.: Kevin Sweeney

Products: EtofenproxtNylar Spot-on Flea and Tick for Dogs EPAReg.#: 2517-RGG

A.I.'s: 

### Ethofenprox (55.0%), Pyriproxyfen (2.2%)

Decision #s: 420097

DPIIs: 371693

Submission: R310, New Products, RD Science Review

MRIDs: Submitted: 47849607,4789608

GLP:. No.



## MRID 47849607:

Title: AnalY$is ofa Dose Titration to Determine the Relationship between Dose Rate of Etofenprox, When Applied as aSpot-On toDogs, and 

### the Duration ofResidual Efficacy Against Flea 

### lInel Tick Reinfestation.

Guideline: 

### OPPTS 810.3300

Materials and Methods:

12 dogs were allocated to 3 treatment groups (4 dogs each, with average size approximately equal, using 30-40 Ib dogs). One was an untreated contrOl group, and the 

### other groups were both: treated with an, etofenprox squeeze on, applied at 2 different dosages (approximately 8g and 4g, respectively). Rates ofa.i. applied to animals were approximately 38 I mglkg and 178 mglkg, re$Pectively. Infestations (andreinfestations over time) were conducted with 50 ticks (R. sanguineus) 

### and 100 cat fleas (c. felis). 

### Fleas were counted via a comb at both 24 hours and 72 hours 

### after each infestationlreinfestatioil. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadeqnate efficacy was shown. % 

### Mortality was calculated in comparison to the control.Regression analysis was conducted to determine ifthere was a significant correlation between treatment dose and duration ofefficacy.
Study Summary ofthe Results;

I. Average flea efficacy was >90% for dogs in the 381 mglkg treatment group through 31 days. For the 178 mglkg treatment, average efficacy was 89% at day 23 and 84% at day 31. 2. Average tick efficacy was 89% for dogs in the 381 mglkg treatment group through 31 days. For the 178 mglkg treatment, average efficacy was only 77% at day 31, but
was adequate through day 23 (96%). 3. There was no significant correlation between dosage and efficacy duration for fleas and ticks, due to insufficient numbers ofdogs. 4. Dose rates in the range of250-300 mglkg were associated with 90% or higher efficacy at 31 days aftertreatment (looking atreinfestations on the 28 th day). This observation can be used to generate a hypothetical dosage schedule for the treatment ofpuppies and dogs 151bs or less, with dogs up to 15lbsreceiving 1.2 

### mL ofa 55% etofenprox product, supporting a claim for the product of "up to 28 days" efficacy against re-infestation with fleas and ticks.
Entomologist's ObservationslDiscussion;

I. Replication was inadequate for the study as typically a minimum of 6 dogs are required for each treatment group. TypiCally, the dogs should be ofvarying breeds and weights, including larger dogs, but this issue isn't as critical for this study, as the proposed product is intended only for small dogs less than 20 Ibs. 2. Efficacy was demonstrated for the 381 mglkg treatment group, but not for the 178 mglkg group. 3. Despite a statistically insignificant relationship between the dosage and the efficacy duration for this product, the authors propose a titration scheme that would support efficacy claims for a product applied at a minimum of250 mglkg a.i. This appears to be supported by the efficacy data for this present study, as dogs treated with this rate and higher were adequately protected for 30 days (albeit an inadequately small sample size). However, according to the study's own titration table, which is a bit confusing, the proposed dose (1.6 mL) appears to be inadequate for dogs larger than 6lbs, because the ai dosage falls below the threshold of250 mglkg.

MRID 47849608:

Title: Analyses ofEfficacy and Safety Datato Support Label Claims for Sergeant's Squeeze-On for Small Dogs Containing Etofenprox and Pyriproxyfen.

This is a summary document ofother studies cited/submitted in support ofthis product.
Entomologist's ObservationslDiscussion: Summarized in other reviews.Efficacy Review

Date: February 12,2010
Efficacy Reviewer: Clayton Myers, Ph.D., Entomolo ist, RD-IB

In 'ers.clavton1lJe a.!Z.ov .\l"A v 703-347-8874 

### 11

Risk Manager Rev.: Kevin Sweeney

Products:

EPA Reg.#:

A.I.'s:

Decision #s:

DP#s:

Submission:

MRIDs:

GLP:

MRID 47849601: EtofenproxlNylar Spot-on Flea and Tick for Dogs

2517-RGG
Ethofenprox (55.0%), Pyriproxyfen (2.2%)

420097

371691
R310, New Products, RD Science Review

Subrrritted: 47849601,47849602,47849603,47849604,47849605, 47849606

No

Title: Efficacy ofa Water-Based Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: OPPTS 810.3300

Materials and Methods: 2 experimental groups ofdogs, 6 dogs in each group, with weights ranging from 4.5-12.2 lbs. One group was a treatment group and one was a control. Treated dogs were dosed with 1.5 mL ofa 55% etofenprox spot-on. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) and 100 cat fleas (C.folis). Fleas were counted at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.

. Study Summary ofthe Results:I. Due to varying dog weights, the effective dose applied ranged between ISO-407 mglkg (mean of231 mglkg). Dogs ranged in weight from 4.S-12.2Ibs. 2. Efficacy against fleas was only adequate through 16 days. 3. Efficacy against ticks was adequate through 31 days (mean efficacy of94%). 4. The dose applied is less than proposed on the label (2.0 mL for dogs 4-20 lbs).

Entomologist's ObservationslDiscussion:

I. While the data support efficacy claims on dogs for ticks through 30 days, the study is limited by the lack ofdogs at the upper margin ofthe weight class, which would be the most likely to have an inadequate level ofcoverage by a 2.0 mL application. 2. Because the rate applied is less than what is proposed on the product label, an approximation can be made based on the titration. For example, if I.S mL is adequate for

a 12 pound dog, then 2.0 mL would only be adequate for dogs up to 16lbs (for ticks only). 3. Flea efficacy was not adequately supported by this study.



### MRID 47849602:

Title: Efficacy, at Minimum Dose Rate, ofan Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: OPPTS 810.3300

Materials and Methods: 17 dogs were allocated to 3 treatment groups (S-6 dogs each). One

was an untreated control group, and the other groups were both treated with an etofenprox squeeze on, applied at 2 different dosages (2 mL and 4 mL, respectively). Dogs were grouped by size so that all dogs received an approximate dosage of250 mglkg ofetofenprox, as a minimum. Group B dogs were all approximately 7-10 Ibs, while Group C dogs were approximately 18-20 lbs. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) and 100 cat fleas (c.ftlis). Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the contro!'
Study Summary ofthe Results:

5. For Group B dogs receiving 2.0 mL oftreatment, flea and tick efficacy is adequate through 22 days after treatment. For Group C dogs receiving 4.0 mL oftreatment, efficacy is adequate through 29 days after treatment.
Entomologist's ObservationslDiscussion:

I. While the study was designed to assess a 'minimum' dosage (250 mg etofenproxlkg animal), this meant that animals at the upper range ofthe the weight classification (i.e.,20 Ib dogs) received a treatment that is approximately double the dose instructed on the product label (2 mL product for dogs weighing 4-20 Ibs). 2. Therefore, dogs in group C were treated with more material than what is on the proposed product label. The data from this study would only support efficacy claims for dogs under 10 Ibs, which received 2 mL per animal, and those claims would only be valid for 22 days after treatment, not a full 30 days.



### MRID 47849603:

Title: Efficacy, at Label Dose Volrune and at Minimum Dose Rate, ofan Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: OPPTS 810.3300

Materials and Methods: 18 dogs were allocated to 3 treatment groups (6 dogs each). One was
an untreated control group, and the other groups were both treated with an etofenprox squeeze on, applied at 2 different dosages (2.5 mL and "4.5 mL, respectively). Dogs were grouped by size. Group B dogs were all approximately 8-9Ibs, while Group C dogs were approximately 18- 20 lbs. Group B dogs were treated with 2.5 mL ofspot-on per animal. Group C dogs were dosed by weight, so that each dog received 247 mg ai/kg, with applications thus varying from 4.3 mL to 4.7 mLper animal Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) and 100 cat fleas (c.felis). Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.

Study Summary ofthe Results:

6. For Group B, flea efficacy was adequate through 16 days after treatment. 7. For Group B, tick efficacy was 89% for 23 days after treatment and 85% for 30 days after treatment. 8. For Group C, flea and tick efficacy was adequate through 30 days after treatment.
Entomologist's ObservationslDiscussion:

1. Both treatment groups were treated with dosages exceeding that proposed on the submitted label, and thus the data are not valid to support efficacy claims for that proposed dosage. 2. For dosages applied as listed in the study, efficacy against fleas in Group B animals was only adequate through 16 days after treatment. Efficacy in Group C was maintained at 89% through 30 days after treatment. 3. For dosages applied as listed in the study, efficacy against ticks in Group B animals was demonstrated to be 89% at 23 days after treatment and 85% at 30 days after treatment. Efficacy in Group C was maintained through 30 days after treatment.MRID 47849604:

Title: Evaluation of Sergeant's Etofenprox Squeeze-on Against Fleas, Ticks, and Mosquitoes on Dogs.

Guideline: OPPTS 810.3300

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on, applied at 2.5 mL per animal. Dogs in the treatment group were all 10 Ibs or less, while control dogs ranged in weight from 11-14.3 Ibs. Infestations (and reinfestations over time) were conducted with 50 each of3 species ofticks (R. sanguineus, D. variabilis, and A. americana) at various infestation intervals, and 100 cat fleas (c.jelis). Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control. In the 3 rd and 4th weeks after treatment, all dogs were anesthetized and confined for 1 hour with 25 unfedAedes aegypti or (separately) with 25 Culex quinquejasciatus mosquitoes, inside a screen cage. Landings were counted for 5 minutes. Dogs were removed after 1 hour and mosquitoes were recovered to assess survival and blood feeding status.
Study Summary ofthe Results:

9. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 10. Flea efficacy was adequate through 23 days after treatment. 11. Tick efficacy was adequate through 16 days after treatment. 12. Treatment was not lethal to either species ofmosquitoes, but inhibited blood feeding >90% (compared to control) for 30 days forAedes and 29 days for Culex.
Entomologist's ObservationslDiscussion:

1. Dogs were treated with dosages exceeding that proposed on the submitted label, and thus the data are not valid to support efficacy claims for that proposed dosage. 2. For dosages applied as listed in the study (2.5 

### rnL), efficacy against fleas is only supported for 23 days after treatment for dogs under 10 Ibs. 3. For dosages applied as listed in the study (2.5 mL), efficacy against ticks is only supported for 16 days after treatment for dogs under 10 Ibs. 4. For the 2.5 mL doses, claims against mosquitoes for prevention ofblood feeding are valid only for dogs less than 10 lbs., and no kills claims are supported for mosquitoes.

MRID 47849605:

Title: Efficacy of Sergeant's Etofenprox Squeeze-on against Ixodes scapularis NymphsGuideline: OPPTS 810.3300

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on, applied at 2.5 mL per animal. Dogs in the treatment group Were all 10 Ibs or less, while control dogs ranged in weight from 11-14.3 Ibs. 3 days after treatment, hair was clipped from each dog. Ten nymphal ticks placed in petri dishes with each hair sample and mortality was assessed at 24 hand 48 h after placement. % Mortality was calculated in comparison to the control.
Study Summary ofthe Results:

13. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 14. Efficacy was 100% for ticks exposed to hair taken 3 days after treatment (I 00% mortality was observed at both 24 h and 48 h after placement on hair).

Entomologist's ObservationslDiscussion:

1. Distribution ofhair samples was not specified, and the randomization scheme was not defined (i.e., were multiple samples pooled for each dog, or were sub-replicates established for each dog?) 2. Because hair was clipped 3 days after treatment, claims against Deer ticks would only be valid for 3 days after treatment. This data would not support the one-month claim proposed on the label. A study that exposed ticks to hair taken 30 days after treatment would be required to demonstrate efficacy against deer ticks.

MRID 47849606:

Title: Efficacy ofa 2 mL Unit Dose of Sergeant's Etofenprox Squeeze-on, Applied at Minimum Dose Rates, against Fleas and Ticks on Small Dogs

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on (55%), applied at 2.0 mL per animal (as proposed on new product label). Dogs in the treatment group Were all 18-20 Ibs., while control dogs ranged in weight from 20-30 Ibs. Infestations (and reinfestations over time) were conducted with 50 each of3 species ofticks(R. sanguineus, D. variabilis, andA. americana) at various Infestation intervals, and 100 cat fleas (C.felis). Fleas

were counted via a comb at both 24 hours and 72 hours after each Infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.
Study Summary ofthe Results:

15. Actual dosages applied to dogs ranged from 122·233 mg ai/kg (mean 127 mg/kg).16. Flea efficacy was adequate through 16 days after treatment and 85% through 23 days after treatment. 17. Tick efficacy was adequate through 23 days after treatment and 80% through 30 days after treatment.

Entomologist's ObservationslDiscussion:

I. This is the only study where the dosage applied to animals exactly matches the dosage on the proposed label, and also used dogs at the upper margin ofthe 20 Ibs. weight class. 2. Efficacy against fleas is only supported for 16 days after treatment and marginally for 23 days after treatment 3. Efficacy against ticks is only supported for 23 days after treatment.

Overall Review ofLabel Claims and Directions:

None ofthe studies were submitted under GLP standards, and protocols were vague on the exact specifications by which parasites were placed on animals (e.g., random anatomical distribution per 810.3300 guideline).

Claims against Deer Ticks, 

### Ixodes, are not supported and must be removed from the label.

Claims against Mosquitoes are not supported for the application rate of2:0 mL proposed on the current label. The dosage would have to be raised to support this claim, and the claim must only be for repellenceisuppression ofmosquito blood feeding. Kills andlor control claims are not supported by the data.

The preponderance ofdata indicates that a 2.0 mL application ofthe proposed 55% etofenprox product is not adequate to protect dogs on the upper end ofthe weight class for the 30 day retreatment interval from fleas and ticks. Ifanimal safety data are adequate, the registrant shonld label the product for different application rates to different weight classes ofdogs. Some variability is evident even when the dosage is raised to 2.5 mL for small dogs Under 10 lbs. For dogs between 10-20 Ibs, the dosage should be raised to 4.5-5.0 mL in order to support the label claims ofcontrol offleas and ticks for 30 days.

Claims against flea eggs and larvae are not supported by this data and must be removed from:jhe label. Also, claims regarding breakage ofthe flea life cycle and prevention offlea eggs from developing for up to 9 weeks (70 days) after application are not supported and also must be removed.

Removal ofunacceptable claims is deferred to the RM reviewer and PM, as some claims may possibly be acceptable under conditional registrations with later submission ofacceptable efficacy data.

### Enclosure 5
Copy ofEPA CASS ReviewUNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

OFFICE OF PREVENTION. PESTICIDES AND TOXIC SUBSTANCES

February 24, 2010



### MEMORANDUM
Subject: Name QfPesticide Product: ETOFENPROXINYLAR SPOT-ON FLEA AND TICRFOR DOGS AND PUPPIES EPA Reg. No. !File Symbol: 

### 2517c RGG DP Barcode: DP 371676 Decision No.: 42Q097 Action Code: R310 PC Codes: 128965 (Etofenprox: 55%) 129032 (pyrlproxyfen: 2.2%)

. From: l3yron T. Backus, Ph.D" Toxicologist 

## (3

# ~ (?

- C • Technical Review Branch 01.-

- 1-"t
- 1-0
, Co

To: Registration Division (7505P)

.

# rf'V

Kevin SweeneylRichard Gebken, RM 13 Insecticide Branch Registration Division (7505P)
Registrant: SERGEANT'S PET CARE PRODUCTS, INC.

. FORMULATION FROM 

### LABEL:

Active Ingredient(s); 128965 Etofenprox 129032 Pyriproxyfim Other Ingredientfs): TOTAL

**ACTION REQVESTED:**  The 

### RiskManager requests:

"

...Please review the attached study and documentation."

Page I of16 Bywt. 55.00%

2.20% 42.80% 100.00%BACKGROUND:

The material received includes a companion animal safety study (in MRlD 47849609) titled: "Companion animal safety evaluation on dogs ofspot-on products containing multiple toxicants and insect growth regulators" as well as a CSF apd a proposed label for the product which would be applied to small and/or toy breed dogs weighing 4-20 lbs. The label dosage rate is given as 2.0 mLldog/application.

COMMENTS AND RECOMMENDATIONS:

1. An Agency contractor, Oak Ridge National Laboratory, conducted the primary review ofthe companion animal safety study. TRB perfonned the secondary review andmade changes as nec·essary.
2. The study is not acceptable to support the proposed use(s) on adult dogs and puppies and cannotbe upgraded. Test groups consisted of6 (3 male and 3 female) adult dogs or puppies. The 870.7200 Companion Animal Safety Guidelines specify that at least 6 animals per sex should be .used at each dosage level. In addition, the adult dogs that were treated with test substance II (containing 55..11;% w/wetofenprox, 8.78% wiwmethoprene, and 2.31 % w/w pyriproxyfen) at 5X theaosage rate weighed (on day -I) 4.06, 7.00, 7.98;8.78, 8.94 and 9.10 kg. Since .only one dog in this gtoup weighedless than 9 lbs 

### ('tOo kg 

## =8.951bs» thedata.couldnot be. used to support thettse of this' formulation on adult dogs we:lg1:iing 4-9 lbs, particularly as the ratio .ofbody surface area to mass could be a motor 

### in absotptionand toxicity. Cumulative dosage rates were 3.08, 3.21, 2.82, 2.56, 2.52 and 2.47 mLlkg (the 4.06 kg dog received a cumulative amount of 12.5 mL test material; the others each received 22.5 mL), with a mean of 2.78 mLlkg; dividing this by 5 (for the 5X margin ofexposlIte) gives 0.555 mLlkg; and dividing 2.0 mL (the proposed dose) by 0.555 mLlkg giVes 3.60 kg (= 7.94lbs), which is also substantially above the proposed 4 lb lower weight limit For the puppies, it is impossible to compare and interpret differences in body weight gains between groups when tjJ.ere was such a range in ages (IQ-lSweeks, with no information as to specific ages for individual animals), the dogs were mixed breed and tjJ.e two heaviest puppies (CC7 692 andCD4 7Ee), which would be expected to showthe greatest weight gains, were both in the control group.
3. TRB considers the behavioral changes (tunning and circling imi:nediately after application of the test substance) in 7 animals (one adult, 6 puppies) as an adverse effect. It is noted that the animals showing behavioral changes were all exposed to test materiallA (8.2(JO/o cypheaothrin, 9,8% fipronil, either in combination with material III, 8.90%methoprene and 2.43% pyriproxyfen, for the one adult, orin combination with material II, 55.16% etofenprox, 8.78% methoprene and 2.31 % pyriproxyfen for the puppies). Although the four puppies in group A2 (receiving 5 applications ofmateriallA and S ofII) showed running and circling only after the first application ofthe test substance and not after the second, third, fourth or fifth application, this may simply be an indication that the application area had been numbed.

4. Refer to the attached DER for additional comments.

Page 2 of 18DATA EVALUATION RECORD
CYPHENOTHRIN, FIPRONIL, ETOFENPROX, METHOPRENE, PYRIPROXIFEN COMPANION ANIMAL SAFETY STUDY- DOGSIPUPPIES

- (OPPTS 870.7200) MRID 47849609

Primary Reviewer: Prepared for
Registration Division Office ofPesticide Programs U.S. Environmental Protection Agency One Potomac Yard 2777 S. Crystal Drive Arlington, VA 22202
Prepared by
Toxicology and Hazard AssessmentGroup Environmental Sciences Division

Oak Ridge National Laboratory OakRidge, TN 37831

Virginia A. Dobow. V.M.D., M.P.H. Signature: Date: Secondary Reviewers: 

### Dana F. GJass, D.V.M. Signature: Date:

Robert H. Ross, M.S., Group Leader Signature: Date: Quality 

### Assurance: Kimberly Slusher, M.S. Signature: Date:

Disclaimer

This review may have been altered subsequentto the contractor's signatures above.

Oak Ridge National Laboratory managed and operated by UT_Battelle, LLC., for the U.S. Department ofEnergy under Contract No. DE_AC05_000R22725.

### EPA Reviewer: Byron T. Backus, Ph.D. Technical Review Branch, Registration Division (750SP) 

### Signature: 

# G 

# ;r5'. (3 •. Q. ? 

### Date: 0 -"1. 

### t - 1-.<>\" Templ.te version 02/06 

# I DATAEVALUATIONRECORD

STUDY TYPE: Companion animal safety study- dogs/puppies

- OPPTS 870.7200

PC CODE: 128965- Ethofenprox, 129032- Pyriproxyfen, DP BARCODE: 371676

TEST MATERIAL (PURITY): Cyphenothrin (8.2% w/w), 

### Fipronil (9.8% rnlw), 

### Etofenprox (55.16% w/w), 

### S-Methoprene (8;78% w/w), 

### Methoprene (8.90% w/w) 

### and Pyriproxifen (2

..31% and 2.43% w/w)



### TRADE NAME: Not provided

CITATION: Delpot:t, P.C. (2009) Companion animal safety evaluation on dogs ofspot-on products containing multiple toJcicl;lllts and insect gI'9wth regulators. CliDVet International (pty) Ltd., Bloemfontein, Republic of South AfriCi!. Study No. CV 08/551, 

### August 6, 2009. MRID 47849609. Unpublished.

SPONSOR: Sergeant's Pet Care Products, Plano, Texas

EXECUTIVESUMMARY: In a companion animal safety study (MRID 47849609), groups of tandom-source adult (> 

### 6 monthsohge) andjuvenile (10-15 weeks ofage) dogs were topically adn:iinistet!:d 3.combinations o.fiDsecticides and insect growth reguli!tofs or one 'inert substance. Two gi-oupsofthreemale and 

### three.fumalejuveniLe dogs 

### were administered test substance IA (8;2% wlw cyphenothrin and 9;8% nilwfiproniJ;' BatchNo. 012003-09) and test substance 

## n (55.16% w/wetofenpfox, 8.78% w/ws-methoprene and 2.31%w/wpyriproJcifen; Batch No. 011901-09) at either IX (recommended dose) or 5X (recommended dose hourly ror 5 applications). Thetestsubstances'were applied simultaneously as adjacent stripes along the dorsum ofthe dog fro1;l 

### behind the ears caudally to the base ofthe tail. Two groups ofthree male and three female adult dogs 'Weighing 9-20 kg were administered the test substance IA and test substance III (8.90% w/w 

### methoprene and 2.43% w/w 

### pyriproxifen; Batcli No. 011902-09) at either IX (recommended dose) or 5X (recommended dose hourly for 5 applications). The test substances were applied as previously described. A group,ofthree male and three female adult dogs weighing less than 9 kg was administered test substance II at 5X (recommended dose houdy ror 5 appliClitions). A group ofthree IIlale and three femalejuvenile dogs and another group ofthree male and three female adult dogs were administered control substance IVA (Batch No. 012004-09) containing inertingredients (not otherwise stated) at5X the recommended dose. The groups and test materials they received are shown in the table below:

Page 4 of 18Group A Group AI (n"'li) Puppies (10.15 weeks) Group A2 (.-6)Puppies (10·IS weeks) Single application ofsubstance lA Fi'vc applications ofsubstance IA Single application ofsubstance II Five applications ofsubstance II

B Group B I (n"'li) Adults (9·20 kg) Group 82 (n-6) Adults (9·20 kg) Group B3 (n"'li) Adults**(~** kg) Single application ofsubstance lA Five appllcations ofsubstance IA**Fiv~** applications ofsubstance II. Single aoolication ofsubstance III Five· applications ofsubstance; III C Group CI (n=6) Puppies (10-15 weeks) , Group C2 (n 6) Adults (9-20 kg) Five applications control subst,ance IVA Five applic.ations control ofsubstance IVA



## , Substance IA contams**8.~%** w/w cyphenothnn and 9.8 Va **rrilw** fiproml. Substance II contains 55.16% **w/w** etofenprox, 8.78% w/w s·methoprene, 2.3 1% **w/w** pyriproxifen. Substance III contains 8.90% methoprene, 2.43% w/w pyriproxifen. CO,Dtrol substance IVA contains inert control substances.
The animals Were observed for clinical signs oftoxicity and dermal irritation for four hours

### postapplication and then twice daily for the dJJration ofthe study (14 days post-application). Body weight, body weight gain, food consumption and clinical pathology parameters (hematology Ilnd clinical chemistry) were measured at the required intervals.

All animals survived to the end ofthe Stlldy. ,Immediately after treatment, one adult dog ,in Group BI (IX applications oftest substances IA and III) showed behavioral changes (running,: circling). This behavioral chllnge was not considered treatment-related in adultS by the sponsor since it was not observed at 5X the recommended dose. Immediately aftet treatment, two puppies in Group AI OX application oftest substances IA and II) showed behavioral changes (running,circl'ing). Four puppies in Group A2 (5X application oftest substances IA and II) showed similar behavioral changes after the first application but not after subsequent applications. These behavioral changes are cOl1$idered to be art adverse effect. White crystallization was observed,on the hair'tips ofmany 

### aduli: ,andjuvenilc::,dogs in the treated and control groups. The application sites ofall dogs in Group BS {5X application oftest'substance IT} had an oily orwet appearance. The ·sign disappeared from one dog onDay +14'but was present on all others at the, end ofthe study.

All adult dogs and puppies'gained weight from Day -I to Day 14. However, meanweight gain in pups in !hetreated, groups (AI and A:l) 

### was 15% lower than the control group pups. The mean weight gain in the treated adult animals (Groups B 1, B2 and B3) was decreased (30-99% as compared to the control group). The difference, relative to controls was largest inthe smaller adult dogs in Group B3 (99% decrease as compared to the control group). Food consumption 

### was not affecte4 by treatiJ:!ent. No treatment-related hematology orclinical chemistzy changes
were observed.

It is noted that the 7 animals (one adult, 6 puppies) that showed behavioral changes {running and circling) immediately,after application of the test substance were all exposedto test material IA (8.20% cyphenothrin, 9.,8% fipronil, either in combination with material ill, 8.90%,methoprene and 2.43% pyriproxyfen, for the one adult, or in combination with material II, 55.16% etofenprox, 8,78% methoprene and 2.31 % pyriproxyfen for the puppies). Although the four puppies 

### in group A2 (receiving 5 applications ofmaterial LA and 5 ofII) showed running and ,circling only after the first application ofthe test substance and not after the second, third, fourth
or fifth application, this may simply be an indication that the application area had been numbed.
Page 5 of\8Test groups consisted of 6 (3 male and 3 female) adult dogs or puppies. The 870.7200 Companion Animal Safety Guidelines specify that at least 6 animals per sex should'be used at each dosage level. In addition, the adult dogs that were treated with test substance II (containing SS.16% w/w etofenprox, 8.78% wlw methoprene, and 2.31% wlw pyriproxyfen) at SX the dosage rate weighed (on day -1) 4.06, 7.00, 7.98, 8.78, 8.,94 and 9.10 kg. Since only one dog in this group weighed less than 91bs (4.06 kg 

### = 8.95 Ibs), the data could not be used to support the use ofthis product/formulation on adult dogs weighing 4-9 Ibs, particularly'as the rlltio ofbody surface area to mass could be a factor in absorption and toxicity. Also, it was not possible to compare body weight changes between adult group B3 (which received the etofenprox-containing formulation) and the control (C2) group because initial mean body weights were so different. For the puppies, it is impossible to compare and interpret differences in body weight gains between groups when there was such a range in ages (10-15 weeks, with no information as to specific ages for individual animals), the dogs were mixed breed andthe two heaviest ,puppies (CC7 692 and CD4 7EC), whil:h would be expected to Show the greatest weight gains, were both in tbe control group.

In addition, it is concluded that the margin ofsafety in puppies administered simultaneous topical application attest substances IA (8.2% wlw cyplienothrin 

### and9;8% m1w 

### fiproilil) and II (55:16% w/w etofenprox, 8.78% wlw s-methoprene and 2.;31% w/wpyriptoxit'en)
was less than IX the recommended dose, based on clinical signs oftoxicity (bebavioral changes immediately post-application).

This companion animal safety study in male and female random-source adult dogs and puppies is, UnacceptablelGnidelineandd!les not satisfy the guideline requil:ement for a companionarumal safety study (OPPTS 870.7200) in the dog and canrtotbe upgraded for either adults orpuppies. See Study Deficiencies section fotdetalls. Major deficiencies include too few' animals per group, failure to testthe end-use product and lack ofsome requil:edreporting,

COMPLIANCE: Signed and dated' OLP, Quality Assurance and Data Confidentiality statements wereprovided for ClinVet International. Pathcare VetarinaryLaboratory, which conducted the hematology and clinical chemistry analyses, is not OLP accredited but is ISO 15189 certified.

Page 6 ofl8I. MATERIALS AND METHODS

A. MATERIALS:

1. Test materials:

1a. Test substance 1 (code name IA) Description: Batch fl.: Purity: Storage: Not provided 012003-09 8.2% W/W cyPhenothrin and 9.8% m/w fipronil*
At room temperature Compound Stability: Expiration date: January 20, 2011 CASH: Not prov!ded

• Batch 2008·Pip.D3. expiration date August 19, 2010, packed_in foil and stored at ambfent temperature, inside carton box. dry

lb. Test substance 2 (code name II) Description: Batch #: Purity: Storage: CompouDdStability: CASH: Not provided 01l901-09 55.16% w/w etofenprox, 8.78% w/w s-mcthoprene,.2.31% W/w**pyriproxif~n** Atroom temperature Expiration date: January 19,2011 Not provided

1c.·Test substance 3 (code naine III) Description: Batch #: Purity: Storage: Compound Stability: CAS#: Not provided 011902-09
8.90% w/w methoprene, 2.43% w!w"pyriproxifen At room**t~~peratUrc** Expiration date: Il!nuary 19. 2011
Not l"avided

1d. Cotttrolsubstance (code·name IVA) Description: Batcb#: Purity: S.orage: Compound Stability: CASH: Not provided 012004-09 Inert control substance (no purity provided) At room temperature Expiration date: II!nDOry 20, 2011 Not provided

2. Vehicle control: See control substance described in 1 d. above.

Page 7 of 18

### 3'. Test animals: Speeies; Strain: Age/weight

Source: Housing: Diet:

Water: Environmental conditions: Temperature: Humlalty: Air changes: Photoperiod: Acclimation period:

B. STUDY DESIGN: Dog Described as "indifferent" Groups AI and A2: 10·15 weeks on day 0 (2.12 -7.32 kg or4.67-l6.14Ibs) Groups Bl and 82: ",6 mos on day 0 (> 9 kgS 20 kg or>19:84IbS 44.09Ibs) Group B3:;:: 6 mos on day 0 ($ 9 kg or:S 19.841b) Group CI: 10·15 weeks on day 0 (2_88 -9.67 kg or 6.35·21.32Ibs) Group C2:" 6 mos on day 0 (> 9 kg S 20 kg or >19.84Ib 544.09lbs) ClinVet International (Pty) Ltd. Colony individuaHy housed in pens Adults (>12 months) were fed a commercial dry dog food (example: ULTRADOG SUPERWOOF DOG FOOD); puppies « 12 months) were fed an "appropriate puppy food" (example: Eukanuba puppy andjunior medium breed) Tap water, ad.libitum

20"4" 

### c Not**pro~rided** 12·15.air cbanges1hr 12 hours Iight/12 hours dark Fourteen days

1. 

### In life dates: Start: March. 19, 2009; End: April 16, 2009

2. Animal assignment: Forty.two animals were-assigned to 

### the study, The genders were separated andthe, dogs allocated to stody groups (Fable 1) Within the body 

### weight requirements using randomization 

### through.**~zation** 

### WiJh body weight as the only criterion. For medium sized adnlt dogs; Within each gender, animals were blocked into tlttee blocks oftbree dogs each. The three heaviest dOgs formed block 1; the next three heaviest dogs fonnedblock 

### :2 and the next three formed block 3. Within blocks, dogs were allocated to one ofthree groups, I, 2 

### or 3. The first animal ofblock 1 was assigned to group I, the second to group 2 and the third to group 3. The first-animal ofblook2 was assigned to group 3, the second to group 2 and the third to group I. The first animal ofblock 3 was assigned to group 1, the second to group 2 and the third to group 3. Groups 1, 2 and 3 wete then randomly assigned to the a'Ctuli1 groups B1, B2 and C using Excel randbetween. Puppies were.similarly assigned to groups AI, A2 and Cl. The six dogs in group B3 were allocated;
no randomization was possible.

Page 8 ofl8Tablel: Stu4y 4esign Group

A Group AI (n=6) Puppies (10-15 weeks) Group A2 (n=6) Puppies (IO-IS weeks) Single application ofsubstance IA Five applications ofsubstance IA Single application ofsubstance 

### rr Five applications ofsubstance II
B Group 8 I (n=6) Adults (9-20 kg) Group B2 (n=6) Adults (9-20 kg) Group 83 (n=6) Adults (<9 kg) Single application ofsubstance lA Five applications ofsubstance lA Five appli.cations ofsubstance 11 Single aooiication ofsubstance I1I Five aoDlications ofsubstance 111 C Group CI**(n~6)** Puppies (IO-IS weeks) Group C2 (n=6) Adults (9-20 kg) Five R-qDlicatiQns COlllTol**SUbS~CCi** lVA 1:?ive applications'control ofsubS1attce IVA

0 

### .. 0 Substance fA contains g.2l-b w/w cyphenothnn and 9.8 j.b m/w fiproml. Substance II contains 55.16% Vi/w etofenproxt 8.78% w/w**s~rneth6prene,** 2.31 % w/w pyriproxif'en. SUbstance III contains 8,90% methoprene, 2.43% w/w pyripro.xifen. Control substance IVA contains inert control substances.
3; nose selection rationale; The·dose rates for test substance IA are based on fipronil and methoprene on the Frontline Plus label and pyriproxyfen in Setgeant's Gold for Dogs. For t\lst substance II, the study report states that the maximum etofenprox smaIl dog dose rate is 758 mg/kg. For test substance Ill, the dose ofpyriproxyfen and s-methoprene is based on Sergeant's Gold for Dogs and Frontline Plus label. However, none ofthe dose rates used is representative ofthe proposed label.

4_ Preparation and treatment: Thetest and control substances were applied as measured doses from syringes (Without needles)toafurrow inthe hair onthe back, starting high ori the neck behind the ears and extending caudally towards the baseofl:he tall. The fur was not shaved or clipped. Technicians applying the substances were blinded to the test material. Test substances lA, II and III Were applied separately as "terminally adjacent stripes, applyiilg test substance IA anterior to test substance II or test substance IA anterior to test substance ill." The placebo control formulation IVA

### was applied separately. Substances lA, II and III Were not.mixed.

Test substances.IA and II were applied as single doses,once only; to the pups intest group A1 and fi,vetimes conseqllently at hourly intervals, each time as a single dose, to the pups in test group A2. SubstancesIA and II were notmixed.

Test substances IA and III were applied as single doses, once.onlY,to theadnlt dogs in group B 1, five times consequently at hourly intervals, eachtime as a single dose, to the adult dogs in group B2. Substances IA and III were not mixed_ Test substanee II was applied five times consequently 

### at hourly intervals, each time as a single dose, to the adult dogs in group B3.

The control substance IVA was applied five times consequently at hourly intervals, each time

as a single dose, to pups and dogs ingroups CI and C2, respectively.

The dose volumes ofthe test and control SUbstances were determined bythe animal's weight

on Day -I (fable 2).

Page 9 ofiS**Tab1.~l:** Doses Groul> TesUllb,lan•• Total dos.admlnistered Al (puppies) IA 0.83

- 2.0 mL (lX) II 3.1 7.5 mL 

### (ix) A2 (puppies) IA 5.0 -13.30mL (1.0 -2.66 mL x 5)



### - II 18.8

- 50.0 mLc3.16 -10.0 mL x5) Bl (adults) IA 1.34 mL (IX) III l.)4mLiIX) B2 (adults) IA 3.4

- 6.7 mL(0.58

- 1.34 mLx 5) III 3.4 - 6.7 mL (0.68 -1.34 mLx 5) B3 adults) II 12.5

- 22.5 mL (2.5

- 4.5 mL x 5) puppies) Cl( IVA l3.IOmL (2.62 mLx 5) C2**.d\ll~)** IVA 5.0 mUl.O mL 

### x5)



### .. Substance lA contains 8.2% w/w cyphenothnn and **9.8%rilJw** tipronlt. Substance **U** contains 55.16% **w/w** etofenprox. 8.78% **w/w** s.methoprencl 2.31% **w/w** pyriproxifcn. Substance

### In COriwns 8.90% metboprene, 2.43% **w/w**pyriproxifen.

. Control substance IVA contains..incrt control substanc.cs. 5. Statistics: The emphasis ofthe statistical analyses was the change from baseline ofeach of thehematololi,Yand clinical chemistry parameters. Individual hematology and clinical chemistry values on 

### test days were tabulated separately for each varillble and each group, together with'the folloWing descriptive statistics: mean, standard deviation (SD), coefficient ofvl!fiatjol1**(~N** 

### %.), geQrnetricmean, geometric SD, minimum, 

### maximum and the n\lltl.bet .of observations: fu the group. The fudividual changes and percentage changes from baseline (test day -3) for each ofthe post-treatrnent days were calcuhited.!!lld tabulated fot each variable and each group. The numbet ofpost-treatment values that fell outside the reference range was calculated. The post-treatment values were compared tothe baselfue values in an intratreatment comparison by means ofan analysis ofvariance (ANOVA) with an animal and observation time as effects. Anintet-treatmentcomparison with respect tothe changes from baseline was also performed. The post-treatment values ofeach the three test treatment groups (BI, B2 and B3) were compared 

### to the col1trol group (C2) for adultdogs. The posttreatment values ofeach ofth.e two test treatrPent groups (AI and A2) were COl11pared 

### to the two controlgrollps (el) for puppies. An analysiS ofcovariance (CO'-AAOVA) wi\:h.a treatment effect and the baseline values 

## as covariate was used. fur the analyseS. fu addition, the change from baselfue values 

### ofeach of the three trea:trnemgroups (Bl, B2 and B3) Wete compared to those ofthe control group (02) ror dogs and the two test groups (AI and A2)
were compared to those of the c6ntrol group (C1) for puppies by means ofan ANOV A with
a treatment effect. Groups AI and A2 were compared in a similar way.
C. METHODS:

1. Observations:

a. Genel'a1.health observations: The anim:als were observed dally for genetai.health. Specific health observations were observed hoUrly onthe day ofapplication until four hours after application ofthe test material and twice daily, thereafter, for the duration of the study. Observations included, but were not limited to, changes in skin and fur, eyes and mucous membranes, nervous signs and behaviorpattern as well as vomiting and diarrhea. Local tolerance observations were also included. Page 10 ofl8

### b. Veterinary examinations: Physioal examinations were conducted by a veterinarian on Days -14, -3, +1, +7 and +14. The examinations included but were not limited to body temperature. pulse rate, auscultation ofthe heart and lungs, mucous membranes and skin. j9ints, eyes, ears, mouth and genital organs

.. 2. Body weight: Animals were weighed on Days -14. -7. -1, +1, +7 and + 14.

3. 

### Food consumption: The amoUllt offood offered was measured and the food consumption
was recorded daily and scored using the following scoring system.

Fc 1- 0-25% 

### Fc 2 - >25- 50% 

### Fc 3 - >50-75% 

### Fc 4 • >75·100%



### 4. Hematology and clinical chemistry: Blood was collected from thejugular vein for hematology and clinical ohemistry·assessments on fasted animals on the following days: • 3.
+1, +7 and +14. The tests were conducted byPathcare. Bloemfontein, South Africa, because ClinVet I11ternational did not have the expertise and apparatus to perfonn the analyses. The CHECKED (X) 

### parameters were examined.

a. Hematology



### x x

.

# M'~n**";'rnJ~j~~:~.;).** X X tiMC)' 

## x '., v61ume (Mev)' X , count 

# -x

x !fur •haseiiOiiOWfS

Page II of 18b. Clinicalchemistrv

ELECTROLYTES OTHER X Calcium'" X Albumin* X Chloride" X Creatinine· Magnesium X 

## Urea nitrogen" X**PhospbQ~s** .. Total Cholesterol. X Potassium· (K) X Globulins· X Sodi\lll1' (NA) X Glucose· ENZYMES (mor. than**~hepatie** enzymes. eg.• ') X Total bilirubin

.. X Alkolirte phosphatase (AP)' X Total protein" Cholinesterase (ChE) Triglycerides

Creatine kinase AlbuminlGlobulin ratio Lactic aero dohy!1rogen

...(LDH) X Direct tlilirubin* X Alanine amirtotransferase (ALT/also SGPl)' I;1dircc:t bilirubin X Aspartaieamino1l"al!sferuc (AST/also SOOT)' BUN1Creatinine ratio GaInmiI. g1utamyl1;ansferoe (ool) TC02 Bicarbo,gate**AnlY~·** Sorbitol dehYdrogenase

.. 

### .. '" Recommended for acompanIon annnal safety evaluation base<l on oPPrs 870.7200

'5. Urinalysis: Urinalysis was J;lot conducted.

6. Sacrifice and pathology: The study did not have a scheduled necropsy.
II. RESULTS

A. ACTUAL. DOSES ADMlNlSTERED: The mglkg doses ofactive ingredients were not calculated. Based oncalculauons·by the EPA reviewer, the IilL/kg doses to puppies were significantly higher than those to adults. For example, adults in Group B I weighing 11.3 to 19.38 kg received 1.34 mL each of.test substances IA and III for a 0.12 to 0.07 mL/kg <lose ofeach substance'. Puppies in Group Al weighing 2.12 to 5.56 kg received 0.83 to 2.0

# mr. Of test substance IA for a 0.36 to 0.39 mLIkg dose, apprOximately 5 times the·adult dose. Puppies in GroupIAreceived 3.1 to 7.5 mL oftest substance 

## n fora 1.34 to 1.46 mLlkg dose, approximately 19 times the adult dog dose.

B. OBSERVATIONS,

1. Clinical sims ortoxicity: Immediately after treatment, one adUlt dog in Group B I showed behavioral changes (running, circling). Ano.ther adult dog in Group 

### 113 had skin irritation on the shaved 

### area ofthe neck (asswned to be 

### area shaved for blood collection). In· Group C2,


### one dog had 

### loose feces 

### three hours post-application, Qne dog had loose mucoid feces with blood on Day +2 and another dog had mucoid feces on Day +2. Minor clinical signs observed in adult dogs after treatment included the following: swollen marrunary gland (Group C2, Days +7 and +14); scab on scrotum (Group C2, Day +14); eczema on neck (Group B3, Day +7); hair loss on chin (Group B3, 

### Days +7 and +14); and right eye lacrimation (Group B2, Day +7). A female in Group BI came into estrus on Day +1.

Page 12 ofiBImmediately after treabnent, two puppies in Group AI showed behavioral changes (running, circling). Four puppies in Group A2 showed similar behavioral changes after the first application but not after subsequent applications. One pup in Group A I had loose feces on Day +1 with blood on Day +4. A pup in Group A2 had loose feces on Day +13. Minor· clinical signs in puppies after treabnent inCluded the followi;lg: thinning ofhair in one pup in Group A2 OnDay +7 which was diagnosed as demodicosis on Day +14; thinning ofhair (Group A2, Day + 14); and scales (two pups in Group C 1, Day + 14). While the demodicosis (mange) was not life threatening, its occUrrence suggests that the overall health ofthe dogs and puppies may have been compromised.

2. Application site examination: White crystallization was observed on the hair tips ofadult

. dogs in Groups Bl [four dogs at one hour post-application and one dog on Day +IJ, B2 (three dogs at one hour post-application, one dog on Day 

### +1 and two dogs on day +2), B3 (two dogs at one hour post-application, four dogs at three hours post-application and one dog at Day +2) and C2 (three dogs at two hours post-application, one dog at3 hours postapplication, one dog at foUt hours post-application and one dog at Day +2). The application sites ofall dagS in Group B3 had an oily or wet appearance. 

### The sign disappeared from one dog onDay +14 but was present an all other dogs.at the end ofthe study.

White crystals were.observed on the hair tips ofpups in Groups Al (two pups atone hour post-application and one pup at three hours**post-appli~tion),** A2 (one pup each at one hour and two hours post-application) and CI (three pups at one hour post-application and one pup at two hours post-application).

3. Mortality: All adult andjuvenile dogs survived to the end ofthe study.

B. BODY WEIGHT.AND WEIGHT GAIN: Body weight data1!I'e presented in Tabid. All adult and

### juvenile dogs gaiI),ed'weightfroinDay--l to Day 14. However, mean weight

# gain in pups in the treated groups CAl and A2) was 15% lower than the control group pups. The
mean weight gain inthetreated adult animals was decreased (30-99% as compared to the control group). The change was largest in the smaller adult-dogs in GrQUP B3 (99% dectease
as compared to the contral group).

Page 13 ofl8Tabl. 3: Mean bod. weighl and body wei.hl •• in'

. Sody w.i.bt (kRl Sod. wei.ht ••in 1<2)**GrQu~** Da.-1 D•• +1' Oay +7' .D•• +14 Da. -I to +1' Dov -I to +7" DaY -1 to +14 Al ·up. 4.24 4.30 4.78 5.44 0.06 0.54 1.20115%)' A2 up, 4.94 5.06 5.S4 6.15 0.12 0.60 1.2[(15%)' CI nuos 5.24 5.50 5.89· 6.66 0.26 0.65 1.42 .81 adults 16.07 16.41 16.63 16.62 0.34 0.56 0.55 30%)C B2 adulls 15.56 15.48 15.75 15.80 -0.08 0.19 0.24 70%)C B3 adults 7.64 7.62 7.62 7.65 -0.02 -0.02 0.01 99%)' C2 adults 16.05 16.30. 16.93 16.84 0.25 0.88 0.79 

## •N "'" 6/group, exceptwhere noted.
b Calculated by the reviewer from data on pages 4647, MRID 47849609

t. Decrease com.pared to .control gro.up

.. calculated by the reviewer" Group Al !)'ealechUXwith Substance IA (8.2% wlw cypfienothrin and 9.8% m!w fipronil) and Substance II (55.16% w/W etofenprox; 8.78% wlw s..mcthoprene, 2'.31 % w/w pyriproXifen) Group A2 treated al5X with Substance 1A(8.2% wlw cyphenothrin and 9.8% m!w fipronil) and Substance II (55.16% wlw elofonprox, 8.78% wlw s-methoprene, 203'I%wlw pyriproxifen) Groups CI and C2.treated· at 5X with Control stibstancc·1VA Group BI treated at IX with SubstancelA (8.2% wlw cyphenotlllin and 9.8% m/w fipronil) and Substance 1lI (8.90% mctboprene,**2.43~** w/w pyriproxifen) GroupB2 treated at 5X with Substance IA (8.2% wlw typhenothrin and 9.8% m!w fipronil) and Substance 111 (8.90% methoprene. 2.43% w/w pyriproxifen)

C. FOOD CONSUMPTION: No treatment-related effects· were reported_

D

.. 'CLINICAL PATHOLOGY ANALYSES:
1_ Hematology: No treatment-related ch!mges were observed in adults or pups_ An increase (as compared to the control group) in monocyte counts in Group BI adult dogs on Day +1 

### was not. considered toxiccilogically significant.

2. Clinical Chemistry: No treatment-related effects were reported in adults or pups. A decrease(as compared 

### to the control group) in creatininein Group B3 on Day +7 and a decrease inASTin Group 

### B3 on Day +14 werenot considetedtoxicolagically Significant. The mean glucose valueinG1;oup A2 

### was increased from baseline (Day -3) to Days +1 and +14_ The 

## mean chloride values in Groups Al and A2 were increased from baseline to Day +7_ These deviations are not considered toxicologically significant.



## m. DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS' CONCLUSIONS: The study author concluded that two test substances, blend IA containing 8.20% w/w cyphenothrin and 9.80% 

## mlw fipronii and blend II containing 55.16% w/wetofenprox, 8_78% w/w s-methoprene and 2.31 % w/w pyriproxifen, were safe to use under the conditions ofthe study when applied simultaneously
as a spot-on to puppies at the recommended dose as well as five times (5X) the recommended dose.

Blend II containing 55.16% w/wetofenprox, 8,78% w/w s-methoprene and 2.31% w/w pyriproxifen, was safe to use under the conditions ofthe study when applied topically to adult dogs at five times the recommended dose. Page 140fI8Two test substances, blQnd IA containing 8.20% w/w cyphenothrin and 10.07% w/w fipromi and blend III contaiIDng 8.90% w/w methoprene and 2..43% w/w pyriproxifen, were safe to
use under the conditions ofthe study when applied simultaneously as a spot-on to adult· dogs at the recqmmended dose as 

### well as at five times the recommende.d dose.

B. REVIEWER COMMENTS: All animals survived to the end ofthe study. Immediately after treatment, one adult dog in Group B1 (IX applications oftest substances IA and III) showed behavioral changes (running, circling). Immediately after treatment, tWo puppies in Group Ai (IX appliqation oftest substanCes 1A and II) showed sirnilarbehavior. Four puppies in Group A2 (5X application oftest substances IA and II) showed the same behavior after the first application but not after subsequent applications. The behavioral signs are considered treatment-related in puppies since they occurred in multiple ammals both at 

### IX and 5X the recommended dose. 

### The behavioral change in adult dogs is considered treatment-related since it also occurred in puppies.

White crystallization was observed on the hair tips ofmany adult and puppies in the**treate~** and control groups. The application Sites ofall dogS in Group B3 (5X application oftest suhstancelI) had an olly or wet**appear~ce.** The signdisappeared from one dog on Day 

### +14 but was present on alI'other dogsattheendofthe study, Since there was· no skin 

### irritation, .theSigns are considered cosmetic. HllWever, the persistence 

## ottest substance IIon the hair of dogs for more 

### thai114 days ls. ofconcern 4ue to potential human exposUre ofowners to 

### pets.

All adult andjuvemle dogs gained weight from Day 

### -I toDay 

### 14. However, mean weight gain inpups in the treated groups (Aland A2) was -15% lower than the control group pups. The change is considered treatment-related. The meanweight gain in the treated adult aillmals (Groups 

### Bl, B2 and B3)was decreased (30-99% as compared to the control group). The change was largest 

### in the smaller adult dogs in Group B3 (99% decrease as compared to the control group). The anirna:ls were considered adults 

### if\hey were >6 months ofage. Adult

. c:iogs usually are not expeeted to change weight in a'14-day period; however, dogs as young as 6 months may still be.gaining weighf. Thebirth. dates of

### the .an1ma:ls were not provided 

### so theirexact'age is unknown. Since the decreases from the control gr-oup were large, the decreased body weigh/gain. is considered treatrnent-relatedin adults. FOod consumption was not affected by treatment. No treatment-related hematology or clinical chermstry changes
were observed.

It is concluded that the margin of safety in puppies administered simultaneous topical applications oftest substances IA (8.2% wlw cyphenothrin and 9.8% mIw fipronil) and II (55.16% wlw etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w pyriproxifen) was less than 1X the recommendell dose; based on clinical signs oftoxicity (behavioral changes imme",iately

### post-application).

It is coneluded that themargin ofsafety in adult dogs (9-20 kg) administered simultaneous topical application oftest substances IA (8.2% w/w cyphenothrin and 9

.•8% mlw fipronil) andIII (8.90% w/w and 2.43% wlw pyriproxifen) was less than IX the recommended dose, based on elinical signs oftoxicity (circling and running in one dog after application). Page 15 ofiSIt 

### is concluded that no Il!argin ofsafety in adult dogs «9 kg) 

### administered 

### a topical application oftest suhstan'ce 

## n (55.16% 

### wfwetofenprox, 8.78% w/w 

### s"methoprene and 2.31 % wlw 

### pynproxlfen) could be established from the findings ofthis study.

. . 

### This study is unacceptable and cannot be upgraded for either adult dogs or puppies.

C. STUDY DEFICIENCIES:



### a. The study report states that the purpose ofthe study is to determine the safety ofa combination ofthree test formulationspot·on products containing three toxicants and two insect growth regulators. The Companion Animal Safety Guideline (OPPTS 870.2700) requires that 

### a study be conducted With the end-use product using the label dose and directions for use,although there is a provision for use ofa max/lox product containing multiple toxicants at the maximum levels which would be anticipated in formulated topical products. However, this does not appear to havebeen the objective ofthe study. It is 

### also unclear why different combinationsof'products were tested in

### adult andjuvenile animals. Pups were administered test substances IA and 

## n, whereas large adult dogs were ru4nhUstered test substances lA.and 

## III and smaller dogs were administered test substance II 

### alone.

b. Other Companion Animal Safety Guideline non-compliances 

### are as follows:

!. 

### The study used three dogs/sex/group, whereas six dogs/sex/group are required. 2. 

### Individual animal data for clinical signs were not provided. 3. 

### Group Qlean 

### values for body weight were not.calculated for Days-14, ·7, +1 and 

### +7. 4. 

### The control formulation 

### is described 

### as "inert control substance". However, it is not certain for Which 

### of tiletest formulatiohS was this the "inert control substance," 

### as no analysis 

## was provided. 5. 

### The date 

### of birth ofthe animals 

### was not provided. 6. Themglkgdose ofactive ingredients was not calculated. 7. 

### The laboratory which conducted the hematology and clinical chemistry testing is not GLP accredited. 8. The Guideline allows furfive hourly applications ofa IX dose to achieve the 5X dose. However, with the large volumes oftest material used on some ofthe smaller animals, it is likely that the material ran offand 

### was not available for abSOrPtion. 9. The study report states that test substances IA, II,and III were applied separately as terminally adjacent stripes, applying .test substance IA anterior to test substance II or test substance lA anterior to 

### test substance III. It is unclear"how the second substance could be applied anteriorly When both were administered from the neck to the base of thetai!. 10. A certificate ofanalysis was not provided for each ofthe 

### test substances. The 

### study report states that

### the concentration ofcyphenothrin in test substance IA should have been 15% as stated in the protocoi but a certificate ofanalysis indicated that it was 8.2%.

Page16of18

### 11. The study author's conclusion (page 56) gives different peroentages offipronil in 

### test substance IA 

### when discussing the findings in 

### puppies (9.8% mlw) 

### and adults (10.07% 

### w/w).

Page 17 oflS\

### ,**~.** 

### DP BARCODE: 371676 2. PCCODES: 128965 (Etofenprox); 129032 (pyriproxyfen) 3. CURRENT DATE: February 24, 2010 4. TEST MATERIALS: Blend IA: 8;20% w/w 

### cyPhenothrin, 9.80% w/w 

### fipronil; Blend II: 55,16% w/wetofenprox, 8.78% w/w 

### methoprene, 2.31 % w/w

### pyriproxyfen; Blend III: 8.90% w/w 

### methoprene, 2.43% w/wpyriproxyfen; BlendIVA: inert control substance
StudylSpecieslLab 

### MRID Results Tox. Core

Study # IDate Cat. Grade Companion Animal Safety StudylDogs & 47849609 Four groups (each 6M & 6F) of NfA U Puppies adult dogs; 3 groups (each 6M & 6F) ofpuppies were used. Adull$: CUnVet International (Ply) Ltd; Group Ell IX lA&ID; Group B2: Bloemfontein, South Africa 5X IA&ID, Group B3: 5X n; Group C2 5X IV A. Puppies: S!tldy CV 08155 I IAugust 6, 2009. GroupAIIXLA≪GroupA2: 5X LA&n;Group CI: 5XIVA. Not pos$ible to ad"'luate!ylllterpret data from design ofsrudy..



# .. Core Grade Key. A**~** Acceptable, S Supplementary; U Unacceptable, W - WaIV!>d

Page 18 ofl8

## of 1t-Y1'(g;}

Recommendation of Division Directors

### ~f1~ Negotiated Due Dates
Decision #: 420097 

# IRegistration #: 2517-RGG 

# IPetition #:

Fee Category: R310 PRlA Decision Time Frame: 6 months

Submitted by: Kevin Sweeney Branch: RDIIB 

# IDate: 3/24/2010 

### Company: Sergeant's Pet Care Products, Inc. Original Due Date: March 31, 2010 

# IProposed New Due Date: April 30,2010
Previous Negotiated Due Dates: None
Is the "Fix" in-house? No If

### not, date "Fix" expected: April 2, 2010 for rebuttal to EPA reviews Issue (describe in detail): Registrant submitted new product to treat "Toy Dogs". They cited a product that is registered for use on cats. The cited product chemistry data were not accepted because they formulated the new product with an alternate formulation ofthe cited product instead ofthe basic formulation. Second, the companion animal safety study (CAS) was determined to be unacceptable. There were deficiencies with the efficacy studies but most ofthose can be resolved with labeling changes and some more efficacy data. The acute toxicology data citations were acceptable. Summary ofDeficiency Type(s): Not Submitted (N) Deficiencies (D) Product Chemistry: (D} Acute Tox:

_ Efficacy: (D} Labeling: (D} Other (describe): (0) 

### Companion Animal Safety Data Describe Interactions with Company (describe when contacted and company's response including response to previous negotiated due dates): Had nUmerous discussions with the registrant over CSF citations in February. On March 2, 2010 all ofthe DERs were sent to the registrant's representative at Exponent and the deficiencies discussed with them. A 75 day letter was sent on March 10, then revised and re-sent on March 22, 2010 with a new 75 day date. The March 10 letter informed them ofthe CAS and efficacy deficiencies. The product chemistry deficiencies were added to the March 22, 2010 letter following an extensive discussion with the Technical Review Branch concerning Confidential State ofFormula (CSF) citations. Met with the registrant face-to-face on March 17 and discussed next steps with the registrant on the telephone on March 19,2010. Registrant submitted extension request on March 23, 2010. They have requested a first extension of only 30 days. No data or rebuttal will be submitted before the PRlA due date ofMarch 31, 2010. Instead, they propose to submit a rebuttal by April 2, 2010. They will also request a meeting at that time to discuss their concerns further.

"75 Day" Letter sent? 03/22/2009 

### (Date sent) Yes No and reason for none?
Rationale for Proposed Due Date:

I 

### Registrant n«#ified that this is the last negotiation? Yes x Not Applicable Approve: 

### \j 

# I Disapprove:

Fonn revised: May 2007If

### disapproved, action to be taken:

: I r I r
### OD or DOD Signatnre\:, \1

## ~ 

# \1 JI Date: ,

- , 

## ,I 

# wl; \\ i 

# .:3'

-3D

- 

# I0

, , 

### \JJJVv ; i 

## \**~** 

### \ 

# \ \jV \ \

Fonn revised: May 2007

# EXponent"

March 23, 2010

Richard Gebken, PM Team 10 Document Processing Desk U.S. Environmental Protection Agency Office ofPesticide Programs (7504P) Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
Subject: Response to EPA Letter Dated March 22, 2010 Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 200)6

telephone 202-772-4900 facsimile 202-772-4979 www.exponent.com

EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies (EPA File Symbol 2517-RGG)

Dear Mr. Gebkin,

On behalfofour client Sergeant's Pet Care Products, Inc. (Sergeant's) (EPA Company Number 2517), Exponent is SUbmitting a response to EPA's 75-day deficiency letter dated March 22, 2010 regarding EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies.

Please find enclosed the following documentation in support ofthis submission:
(I) Application for Pesticide Form (8570-1).

At this time, Sergeant's is notifYing the Agency that it plans to continue supporting this pending registration application. The current PRIA due date is March 31, 2010. Based upon EPA's recent letter iUs our understanding.thatadditional time 

### will be needed by EPAand Sergeant's to further review this pending application. Sergeant's requests an initial 30-day PRIA extension. We believe this 30-day extension will be sufficient for the Agency and Sergeant's to review our initial response to the EPA letter.
Sergeant's strategy is to submit a written rebuttal to EPA by April 2, 2010. This letter will address the issues identified in the Agency's deficiency letter ofMarch 22, 2010. In addition, Sergeant's will submit product-specific product chemistry data to EPA to support this product registration. Once all ofthe above information is submitted to EPA, Sergeant's requests to meet with EPA to discuss the support data in detail.
Sergeant's intends to request a meeting with appropriate EPA staffto discuss our submission in April. We will submit a separate meeting request letter to you with our submission.If after we meet with the Agency there is a need to extend the PRIA date, Sergeant's will submit

a second PRIA extension request to EPA.

Ifyou have any questions, please contact me at 202-772-4932.
Sincerely,



## -..

# ~~l/**IJ~<~lbL/CL))** James Messina Authorized Representative of

Sergeant's Pet Care Products, Inc.

Enclosure

cc: Kevin Sweeney, EPA Kelly Hoskins, Sergeant's Larry Nouvel, Sergeant's Rick Tinsworth, ExponentPlease read instructions on reverse before completing form. Form Approved. OMS No. 2070-0060. Approval expires 05-31-98
United States

### ~_Registration OPP Identifier Number 

# EPA Environ'mental Protection Agency D_Amendment Washington, DC 20460 D Other
Application for Pesticide· Section I
1.**com~5~y/product** Number 2. EPA Product Manager 3. Proposed Classification 2 17-RGG R. Gebken 4. Company/Product (Name) PM# DNone 

# D EtofenproxINylar Spot-On Flea and Tick for Dogs and Puppies PM-10 Restrlcted 5. Name and Address of Applicant (Include ZIP Code) 6. Expedited Review. In accordance with FIFRASection 3(C)(3)(b)(I), my Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to: 2637 South 158th Plaza, Suite 100 Omaha, NE 68130-1703 EPA Reg. No.

Product Name 

# o Check ifthis is a new address Section II 

# D Amendment

- Explain below. 

# D Final printed labels in response to Agency letter dated XX-XX-XX

### ~ Resubmission in response to Agency letter dated 3-22-10 D "Me Too" Application 

# D Notification

- Explain below. 

# D Other

- Explain below. Explanation: Use additional page(s) if necessary. (For section I and Section II.) Submission in response to EPA leHer dated March 22, 2010, requestto extend PRIA due date.

Section III

1. Material This Product Will Be Packaaed In: Child-Resistant Packaging Unit Packaging Water Soluble Packaging 2. Type of Container DYes' DYes DYes 

# o Metal DNo 

# o No 

# o No 

# o Plastic If "Yes" No. per If "Yes" No. per DGlass 'Certification must Unit Packaging wgt. Container Package wgt. Container DPaper be submitted 

## I I DOther (Specify) Plastic Bag 3. Location of Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions DLabel 

# o Container TBD DOn Can Don Labeling accompanying product
6. Manner in Which Label is Affixed to Product gLithOgraPh DOther**~-.-,-----~--** _._-----_._--- ..

## __.- .._._.,---- 

### ----0------------.---

---------- - -- Paper glued DStenciled Section IV
1. Contact Point (Como/ete items directly be/ow foridentification ofindividual to be contacted, ifnecessary, to DrDCesS this aDDlicationJ Name Title Telephone No. (include Area Code) James Messina Authorized Representative 202-772·4932
Certification 6. Date Application I certify that the statements I have made on this fOlm and aI/ attachments thereto are tlue, accU/ate and complete. I Received acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both (Stamped) under applicable law,**2_Sign~ ~** 

# /{~~ 3. Title

## ~,~ Authorized Representative

4. Typed Name: James Messina 5. Date: March 23, 2010

### DATE OUT: 02/01110



### SUBJECT: FEE PRODUCT CHEMISTRY REVIEW OF MP [I 

### EP [XI 

### DP BARCODE No.: D371682 REG. No. **IFile** 

### Symbol No. 2517-RGG PRODUCT NAME: ETOFENPROXYINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES PCC: 129032,128965 FOOD USE 

### [I Decision No. 420097

COMPANY: SEARGANT'S PET CARE PRODUCTS, INC.

FROM: 

## \ A 

# -v\v"v\ '

..

## ~ . \\0

## ~di crairola, Chemist Product Chemistry Team Technical Review BranchiRD (7505P)

TO: Kevin SweeneylRichard Gebken PM 13 Insecticide BranchiRD (7505P)

INTRODUCTION:

SEARGANT'S PET CARE PRODUCTS, INC. is seeking registration for the subject product ETOFENPROXYINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES. Applicant has submitted a Basic and Alternate CSF both dated 09/10109. 

### Applicant claims the product to be a "Me Too" ofEPA Reg. # 69332-3. The submitted package was reviewed and details will be discussed below:

SUMMARY OF FINDINGS:

I. 

### The subject ETOFENPROXYINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES contains 55.0% ofEtofenprox and 2.2% ofPyriproxyfen.

2. SEARGANT'S PET CARE PRODUCTS, INC. has cited MRID #s 461613-01,-02 and 467008-01 for Product Chemistry data to support the registration of ETOFENPROXYINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES.

3. The sources ofactive ingredients listed for the subject product are registered.

4. Basic and Alternate CSF both dated 09110109 

### meet the label claim of55.0% ofEtofenprox and 2.2% ofPyriproxyfen.5. Inerts used are approved for non-food use.

6. The subject product is not identical to EPA Reg. # # 69332-3 from product chemistry point ofview, product chemistry data cannot be cited. Product chemistry product specific data for the proposed new product must be submitted.



### CONCLUSIONS:

TRB has reviewed the aforementioned product chemistry data submitted for the above mentioned subject product and has concluded that:

1. The subject product ETOFENPROXY INYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES contains 55.0% ofEtofenprox and 2.2% ofPyriproxyfen.

2. Basic and Altemate CSF both dated 0911 0/09 are found acceptable.

3. The label claim is in compliance with PR Notice 91-2.

4. Product Chemistry to support the registration ofETOFENPROXY INYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES cannot be cited. Product chemistry product specific data for the proposed new product must be submitted.

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460-0001



### Mr. James B. 

### Messina Authorized Representative of Sergeant's Pet Care Products, Inc. Exponent 1130 Connecticut Avenue, NW Suite 110 Washington, DC 20036
Subject: 

### New Product Registration (R31 0) EPA File Symbol: 2517-RGG OFFICE of PREVENTION, PESTICIDES AND TOXIC SUBSTANCES



### MAR 2 2 2010

Product Name: EtofenproxlNylar Spot-on Flea and Tick for Dogs and Puppies Date ofSubmission: September 10,2009

Dear Mr. Messina:

The application referred to above has been determined, pursuant to 40 CFR 

### §152.1 05, not to be sufficiently complete to process. Therefore, the application is considered deficient. The companion animal safety study is unacceptable and there are a number ofdeficiencies in the product performance studies. You must address these deficiencies, as detailed below, within 75. days ofthe date ofthis letter, before the processing ofthe application can be continued.

If, after 75 days, you do not respond, or you subsequently fail to complete the application within the time scheduled for completion as noted below, the Agency will terminate any action on this application and will treat the application as ifit has been withdrawn by the applicant. Any subsequent submission relating to this application must be submitted as a new application.

The noted deficiencies for this R31 0 new product; non-fast track application are highlighted below. Details can be found in the Data Evaluation Reports (DERs) I sent to you on March 2,2010.

1. The companion animal safety study (MRID 47849609) is unacceptable and cannot be upgraded.

2. The basic formulation ofyour product is not similar to the basic formulation ofthe cited product. Therefore, you must generate product specific chemistry data on your product. Citing an alternate formulation does not relieve you from the product specific chemistry data requirement because the product chemistry data for every product has been generated from the basic formulation only.

3. The product performance DERs identified problems in the submitted studies with replication, dosage,

### and study design.

The PRIA due date for this product is March 31, 2010. For reference purposes, the timeline for your response (provided an extension of the PRIA due date is granted) is June 6, 2010. Ifyou have not responded, or you subsequently failed to complete the application within the time scheduled for completion, the Agency will terminate any action on the application, and will treat the application as ifit has been withdrawn.

If you have any questions, please contact Kevin Sweeney at (703) 305-5063 or via e-mail at sweeney.kevin@epa.gov 

### Thank you for your cooperation in this matter.

S!ncerely, ,1
1.1

## ~. {\. it / 

# /**U~·**

# -'~rt;



# ·vL.----.l '**c.~** / / I 

## 0**'-p~ ~ic**  'd 1. 

### Gebken, Product Manager Insecticide Branch, Registration Division (7505P)

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460-0001

Mr. James B. Messina Authorized Representative of Sergeant's Pet Care Products, Inc. Exponent 1130 Connecticut Avenue, NW Suite 110 Washington, DC 20036


### Subject: New Product Registration (R31 0) EPA File Symbol: 2517-RGG OFFICE of PREVENTION, PESTICIDES AND TOXIC SUBSTANCES



### MAR 1 0 2010

Product Name: EtofenproxlNylar Spot-on Flea and Tick for Dogs and Puppies Date of Submission: September 10, 2009

Dear Mr. Messina:

The application referred to above has been determined, pursuant to 40 CFR 

### §152.1 05, not to be sufficiently complete to process. Therefore, the application is considered deficient. The companion animal safety study is unacceptable and there are a number ofdeficiencies in the product performance studies. You must address these deficiencies, as detailed below, within 75 days ofthe date ofthis letter, before the processing ofthe application can be continued.

If, after 75 days, you do not respond, or you subsequently fail to complete the application within the time scheduled for completion as noted below, the Agency will terminate any action on this application and will treat the application as ifit has been withdrawn by the applicant. Any subsequent submission relating to this application must be submitted as a new application.

The noted deficiencies for this R31 0 new product; non-fast track application are highlighted below. Details can be found in the Data Evaluation Reports (DERs) I sent to you on March 2, 20IO.

1. The companion animal safety study (MRID 47849609) is unacceptable and cannot be upgraded.

2. The product performance DERs identified problems in the submitted studies with replication, dosage, and study design.

### The PRIA due date for this product is March 31, 2010. For reference purposes, the timeline for your response (provided an extension ofthe PRIA due date is granted) is May 25, 2010. 

### Ifyou have not responded, or you subsequently failed to complete the application within the time scheduled for completion, the Agency will terminate any action on the application, and will treat the application as ifit has been withdrawn.

If you have any questions, please contact Kevin Sweeney at (703) 305-5063 or via e-mail at sweeney.kevin@epa.gov 

### Thank: you for your cooperation in 

### this matter.

Sincerely, 

### n 

# I 

# '\-**(\1~'** i

# " 

# I

! 

### ',')I,-JXi 

# I

',./**~-** ,I 

# -, C-, !

# '~ , Ri<l,birrd

# Jd ebken, C Product Manager Insecticide Branch, Registration Division (7505P)Efficacy Review

Date: February 12,2010
Efficacy Reviewer:

Risk Manager Rev.: Kevin Sweeney

Products: EtofenproxINy1ar Spot-on Flea and Tick for Dogs

EPA Reg. #: 2517-RGG

A.I.'s: Ethofenprox (55.0%), Pyriproxyfen (2.2%)

Decision #s: 420097

DP#s: 371693

Submission: R31 0, New Products, RD Science Review

MRIDs: Submitted: 47849607,4789608



### GLP: No

MRID 47849607:

Title: Analysis ofa Dose Titration to Determine the Relationship between Dose Rate of Etofenprox, When Applied as a Spot-On to Dogs, and the Duration ofResidual Efficacy Against Flea and Tick Reinfestation.



### Guideline: OPPTS 810.3300

Materials and Methods:

12 dogs were allocated to 3 treatment groups (4 dogs each, with average size approximately equal, using 30-40 Ib dogs). One was an untreated control group, and the other groups were both treated with an etofenprox squeeze on, applied at 2 different dosages (approximately 8g and 4g, respectively). Rates ofa.i. applied to animals were approximately 381 mg/kg and 178 mg/kg, respectively. Infestations (andreinfestations over time) were conducted with 50 ticks (R. 

### sanguineus) and 100 cat fleas (c.

### felis). Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.

### Regression analysis was conducted to detennine ifthere was a significant correlation between treatment dose and duration ofefficacy.


### Study Summary ofthe Results:

1. Average flea efficacy was >90% for dogs in the 381 mg/kg treatment group through 31 days. For the 178 mg/kg treatment, average efficacy was 89% at day 23 and 84% at day 31. 2. Average tick efficacy was 89% for dogs in the 381 mg/kg treatment group through 31 days. For the 178 mg/kg treatment, average efficacy was only 77% at day 31, but

was adequate through day 23 (96%). 3. There was no significant correlation between dosage and efficacy duration for fleas and ticks, due to insufficient numbers ofdogs. 4. Dose rates in the range of250-300 mg/kg were associated with 90% or higher efficacy at 31 days after treatment (looking at reinfestations on the 28th 

### day). This observation can be used to generate a hypothetical dosage schedule for the treatment ofpuppies and dogs 151bs or less, with dogs up to 15 Ibs receiving 1.2 mL ofa 55% etofenprox product, supporting a claim for the product of"up to 28 days" efficacy against re-infestation with fleas and ticks.


### Entomologist's ObservationslDiscussion:

I. Replication was inadequate for the study as typically a minimum of6 dogs are required for each treatment group. Typically, the dogs should be ofvarying breeds and weights, including larger dogs, but this issue isn't as critical for this study, as the proposed product is intended only for small dogs less than 20 lbs. 2. Efficacy was demonstrated for the 381 mg/kg treatment group, but not for the 178 mg/kg group. 3. Despite a statistically insignificant relationship between the dosage and the efficacy duration for this product, the authors propose a titration scheme that would support efficacy claims for a product applied at a minimum of250 mg/kg a.i. This appears to be supported by the efficacy data for this present study, as dogs treated with this rate and higher were adequately protected for 30 days (albeit an inadequately small sample size). However, according to the study's own titration table, which is a bit confusing, the proposed dose (1.6 mL) appears to be inadequate for dogs larger than 6lbs, because the ai dosage falls below the threshold of250 mg/kg.

MRiD 

### 47849608:

Title: Analyses ofEfficacy and Safety Data to Support Label Claims for Sergeant's Squeeze-On for Small Dogs Containing Etofenprox and Pyriproxyfen.

This is a summary document ofother studies cited/submitted in support ofthis product.
Entomologist's Observations/Discussion: Summarized in other reviews.

### Efficacy Review

Date: 

### February 12,2010
Efficacy Reviewer:

Risk Manager Rev.: 

### Kevin Sweeney

Products:



### EPA Reg. #:



### A.I.'s:

Decision #s:



### DP#s:

Submission:

MRIDs:

GLP:



### MRID 47849601: 

### EtofenproxlNylar Spot-on Flea and Tick for Dogs

2517-RGG
Ethofenprox (55.0%), Pyriproxyfen (2.2%)

420097

371691

R31 0, New Products, RD 

### Science Review

Submitted:

No 47849601,47849602,47849603,47849604,47849605, 47849606

Title: 

### Efficacy of a Water-Based Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: 

### OPPTS 810.3300

Materials and Methods: 

### 2 experimental groups ofdogs, 6 dogs in each group, with weights ranging from 4.5-12.2Ibs. One group was a treatment group and one was a control. Treated dogs were dosed with 1.5 mL ofa 55% etofenprox spot-on. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) 

### and 100 cat fleas (c.

### felis). 

### Fleas were counted at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.
Study Summary ofthe Results:

### I. Due to varying dog weights, the effective dose applied ranged between 150-407 mg/kg (mean of231 mg/kg). Dogs ranged in weight from 4.5-12.2 lbs. 2. Efficacy against fleas was only adequate through 16 days. 3. Efficacy against ticks was adequate through 31 days (mean efficacy of 94%). 4. The dose applied is less than proposed on the label (2.0 mL for dogs 4-20 Ibs).

Entomologist's Observationsilliscussion:

I. 

### While the data support efficacy claims on dogs for ticks through 30 days, the study is limited by the lack ofdogs at the upper margin ofthe weight class, which would be the most likely to have an inadequate level of coverage by a 2.0 mL application. 2. Because the rate applied is less than what is proposed on the product label, an approximation can be made based on the titration. For example, if 1.5 mL is adequate for

a 12 pound dog, then 2.0 mL would only be adequate for dogs up to 16lbs (for ticks only). 3. Flea efficacy was not adequately supported by this study.

MRID 47849602:



### Title: Efficacy, at Minimum Dose Rate, of an Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: 

### OPPTS 810.3300

Materials and Methods: 17 dogs were allocated to 3 treatment groups (5-6 dogs each). One

was an untreated control group, and the other groups were both treated with an etofenprox squeeze on, applied at 2 different dosages (2 mL and 4 mL, respectively). Dogs were grouped by size so that all dogs received an approximate dosage of250 mg/kg ofetofenprox, as a minimum. Group B dogs were all approximately 7-10 lbs, while Group C dogs were approximately 18-20 lbs. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) 

### and 100 cat fleas (c.felis). 

### Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.
Study Summary ofthe Results:

5. For Group B dogs receiving 2.0 mL oftreatrnent, flea and tick efficacy is adequate through 22 days after treatment. For Group C dogs receiving 4.0 mL oftreatrnent, efficacy is adequate through 29 days after treatment.
Entomologist's Observationsilliscussion:

I. While the study was designed to assess a 'minimum' dosage (250 mg etofenprox/kg animal), this meant that animals at the upper range ofthe the weight classification (i.e.,

### 20 Ib dogs) received a treatment that is approximately double the dose instructed on the product label (2 mL product for dogs weighing 4-20 Ibs). 2. Therefore, dogs in group C were treated with more material than what is on the proposed product label. The data from this study would only support efficacy claims for dogs under 10 Ibs, which received 2 mL per animal, and those claims would only be valid for 22 days after treatment, not a full 30 days.

MRID 47849603:



### Title: Efficacy, at Label Dose Volume and at Minimum Dose Rate, of an Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: 

### OPPTS 810.3300

Materials and Methods: 18 dogs were allocated to 3 treatment groups (6 dogs each). One was
an untreated control group, and the other groups were both treated with an etofenprox squeeze on, applied at 2 different dosages (2.5 mL and -4.5 mL, respectively). Dogs were grouped by size. Group B dogs were all approximately 8-9 lbs, while Group C dogs were approximately 18- 201bs. Group B dogs were treated with 2.5 mL of spot-on per animal. Group C dogs were dosed by weight, so that each dog received 247 mg ai/kg, with applications thus varying from 4.3 mL to 4.7 mL per animal Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) 

### and 100 cat fleas (c.

### fe/is). 

### Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.

Stndy Summary ofthe Results:

6. For Group B, flea efficacy was adequate through 16 days after treatment. 7. For Group B, tick efficacy was 89% for 23 days after treatment and 85% for 30 days after treatment. 8. For Group C, flea and tick efficacy was adequate through 30 days after treatment.
Entomologist's ObservationslDiscussion:

1. Both treatment groups were treated with dosages exceeding that proposed on the submitted label, and thus the data are not valid to support efficacy claims for that proposed dosage. 2. For dosages applied as listed in the study, efficacy against fleas in Group B animals was only adequate through 16 days after treatment. Efficacy in Group C was maintained at 89% through 30 days after treatment. 3. For dosages applied as listed in the study, efficacy against ticks in Group B animals was demonstrated to be 89% at 23 days after treatment and 85% at 30 days after treatment. Efficacy in Group C was maintained through 30 days after treatment.MRID 47849604:

Title: Evaluation of Sergeant's Etofenprox Squeeze-on Against Fleas, Ticks, and Mosquitoes on Dogs.



### Guideline: OPPTS 810.3300

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on, applied at 2.5 mL per animal. Dogs in the treatment group were all 10 lbs or less, while control dogs ranged in weight from 11-14.3 lbs. Infestations (and reinfestations over time) were conducted with 50 each of3 species ofticks 

### (R. sanguineus, D. variabilis, and 

### A. americana) at various infestation intervals, and 100 cat fleas (c.

### felis). Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control. 

### In the 3 rd and 4th weeks after treatment, all dogs were anesthetized and confined for I hour with 25 unfed 

### Aedes aegypti or (separately) with 25 

### Culex quinquefasciatus mosquitoes, inside a screen cage. Landings were counted for 5 minutes. Dogs were removed after I hour and mosquitoes were recovered to assess survival and blood feeding status.
Study Summary ofthe Results:

9. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 10. Flea efficacy was adequate through 23 days after treatment. II. Tick efficacy was adequate through 16 days after treatment. 12. Treatment was not lethal to either species ofmosquitoes, but inhibited blood feeding >90% (compared to control) for 30 days for 

### Aedes and 29 days for 

### Culex.
Entomologist's ObservationslDiscussion:

I. Dogs were treated with dosages exceeding that proposed on the submitted label, and thus the data are not valid to support efficacy claims for that proposed dosage. 2. For dosages applied as listed in the study (2.5 mL), efficacy against fleas is only supported for 23 days after treatment for dogs under 10 lbs. 3. For dosages applied as listed in the study (2.5 mL), efficacy against ticks is only supported for 16 days after treatment for dogs under 10 lbs. 4. For the 2.5 mL doses, claims against mosquitoes for prevention ofblood feeding are valid only for dogs less than 10 lbs., and no kills claims are supported for mosquitoes.

MRID 47849605:

Title: Efficacy of Sergeant's Etofenprox Squeeze-on against 

### Ixodes scapu/aris Nymphs

### Guideline: OPPTS 810.3300

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on, applied at 2.5 mL per animal. Dogs in the treatment group were all 10 Ibs or less, while control dogs ranged in weight from 11-14.3 Ibs. 3 days after treatment, hair was clipped from each dog. Ten nymphal ticks placed in petri dishes with each hair sample and mortality was assessed at 24 hand 48 h after placement. % Mortality was calculated in comparison to the control.
Study Summary ofthe Results:

13. Actual dosages applied to dogs ranged from 304-411 mg ailkg. 14. Efficacy was 100% for ticks exposed to hair taken 3 days after treatment (100% mortality was observed at both 24 hand 48 h after placement on hair).

Entomologist's ObservationslDiscussion:

I. Distribution ofhair samples was not specified, and the randomization scheme was not defined (i.e., were multiple samples pooled for each dog, or were sub-replicates established for each dog?) 2. Because hair was clipped 3 days after treatment, claims against Deer ticks would only be valid for 3 days after treatment. This data would not support the one-month claim proposed on the label. A study that exposed ticks to hair taken 30 days after treatment would be required to demonstrate efficacy against deer ticks.

MRID 47849606:

Title: Efficacy of a 2 mL Unit Dose of Sergeant's Etofenprox Squeeze-on, Applied at Minimum Dose Rates, against Fleas and Ticks on Small Dogs

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on (55%), applied at 2.0 mL per animal (as proposed on new product label). Dogs in the treatment group were all 18-20 Ibs., while control dogs ranged in weight from 20-30 Ibs. Infestations (and reinfestations over time) were conducted with 50 each of3 species ofticks 

### (R. sanguineus, D. variabilis, andA. 

### americana) at various infestation intervals, and 100 cat fleas 

### (C.felis). Fleas

were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.
Study Summary ofthe Results:

15. Actual dosages applied to dogs ranged from 122-233 mg ai/kg (mean 127 mg/kg).

### 16. Flea efficacy was adequate through 16 days after treatment and 85% through 23 days after treatment. 17. Tick efficacy was adequate through 23 days after treatment and 80% through 30 days after treatment.

Entomologist's ObservationslDiscussion:

I. This is the only study where the dosage applied to animals exactly matches the dosage on the proposed label, and also used dogs at the upper margin ofthe 20 lbs. weight class. 2. Efficacy against fleas is only supported for 16 days after treatment and marginally for 23 days after treatment 3. Efficacy against ticks is only supported for 23 days after treatment.

Overall Review ofLabel Claims and Directions:

None ofthe studies were submitted under GLP standards, and protocols were vague on the exact specifications by which parasites were placed on animals (e.g., random anatomical distribution per 810.3300 guideline).

Claims against Deer Ticks, Ixodes, are not supported and must be removed from the label.

Claims against Mosquitoes are not supported for the application rate of2.0 mL proposed on the current label. The dosage would have to be raised to support this claim, and the claim must only be for repellence/suppression ofmosquito blood feeding. Kills and/or control claims are not supported by the data.

The preponderance ofdata indicates that a 2.0 mL application ofthe proposed 55% etofenprox product is not adequate to protect dogs on the upper end ofthe weight class for the 30 day retreatment interval from fleas and ticks. If animal safety data are adequate, the registrant should label the product for different application rates to different weight classes of dogs. Some variability is evident even when the dosage is raised to 2.5 mL for small dogs under 10 lbs. For dogs between 10-20 Ibs, the dosage should be raised to 4.5-5.0 mL in 

### order to support the label claims ofcontrol offleas and ticks for 30 days.

Claims against flea eggs and larvae are not supported by this data and must be removed from the label. Also, claims regarding breakage ofthe flea life cycle and prevention offlea eggs from developing for up to 9 weeks (70 days) after application are not supported and also must be removed.

Removal ofunacceptable claims is deferred to the RM reviewer and PM, as some claims may possibly be acceptable under conditional registrations with later submission ofacceptable efficacy data.Efficacy Review

Date: 

### February 12,2010
Efficacy Reviewer: 

### Clayton Myers, PhD., Entomologis

m ers.c1a on e a. 0'-' 

### 703-347-8874

Risk Manager Rev.: 

### Kevin Sweeney

Products: 

### EtofenproxlNylar Spot-on Flea and Tick for Dogs

EPA Reg. #: 

### 2517-RGG

A.I.'s: 

### Ethofenprox (55.0%), Pyriproxyfen (2.2%)

Decision 

### #s: 420097

DP#s: 

### 371693

Submission: 

### R31 0, New Products, RD 

### Science Review

MRIDs: 

### Submitted: 47849607,4789608

GLP: 

### No

MRID 47849607:

Title: 

### Analysis ofa Dose Titration to Determine the Relationship between Dose Rate of Etofenprox, When Applied as a Spot-On to Dogs, and the Duration ofResidual Efficacy Against Flea and Tick Reinfestation.

Guideline: 

### OPPTS 810.3300

Materials and Methods:



### 12 dogs were allocated to 3 treatment groups (4 dogs each, with average size approximately equal, using 30-40 lb dogs). One was an untreated control group, and the other groups were both treated with an etofenprox squeeze on, applied at 2 different dosages (approximately 8g and 4g, respectively). Rates ofa.i. applied to animals were approximately 381 mg/kg and 178 mglkg, 

### respectively. Infestations (andreinfestations over time) were conducted with 50 ticks (R. 

### sanguineus) 

### and 100 cat fleas (c.

### felis). 

### Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.

### Regression analysis was conducted to determine ifthere was a significant correlation between treatment dose and duration ofefficacy.
Study Summary ofthe Results:

1. Average flea efficacy was >90% for dogs in the 381 mg/kg treatment group through 31 days. For the 178 mg/kg treatment, average efficacy was 89% at day 23 and 84% at day 31. 2. Average tick efficacy was 89% for dogs in the 381 mg/kg treatment group through 31 days. For the 178 mg/kg treatment, average efficacy was only 77% at day 31, but

was adequate through day 23 (96%). 3. There was no significant correlation between dosage and efficacy duration for fleas and ticks, due to insufficient numbers ofdogs. 4. Dose rates in the range of250-300 mglkg 

### were associated with 90% or higher efficacy at 31 days after treatment (looking at reinfestations on the 28 th 

### day). This observation can be used to generate a hypothetical dosage schedule for the treatment ofpuppies and dogs 151bs or less, with dogs up to 15 Ibs receiving 1.2 mL ofa 55% etofenprox product, supporting a claim for the product of"up to 28 days" efficacy against re-infestation with fleas and ticks.
Entomologist's ObservationslDiscussion:

1. Replication was inadequate for the study as typically a minimum of6 dogs are required for each treatment group. Typically, the dogs should be ofvarying breeds and weights, including larger dogs, but this issue isn't as critical for this study, as the proposed product is intended only for small dogs less than 20 Ibs. 2. Efficacy was demonstrated for the 381 mg/kg treatment group, but not for the 178 mg/kg group. 3. Despite a statistically insignificant relationship between the dosage and the efficacy duration for this product, the authors propose a titration scheme that would support efficacy claims for a product applied at a minimum of250 mg/kg a.i. This appears to be supported by the efficacy data for this present study, as dogs treated with this rate and higher were adequately protected for 30 days (albeit an inadequately small sample size). However, according to the study'S own titration table, which is a bit confusing, the proposed dose (1.6 mL) appears to be inadequate for dogs larger than 6 Ibs, because the ai dosage falls below the threshold of250 mglkg.



### MRID 47849608:

Title: Analyses ofEfficacy and Safety Data to Support Label Claims for Sergeant's Squeeze-On for Small Dogs Containing Etofenprox and Pyriproxyfen.

This is a summary document ofother studies cited/submitted in support ofthis product.
Entomologist's ObservationslDiscussion: Summarized in other reviews.Efficacy Review

Date: 

### February 12,2010
Efficacy Reviewer:

Risk Manager Rev.: 

### Kevin Sweeney

Products: 

### EtofenproxlNylar Spot-on Flea and Tick for Dogs

EPA Reg. #: 

### 2517-RGG

A.I. 

### 's: Ethofenprox (55.0%), Pyriproxyfen (2.2%)

Decision 

### #s: 420097

DP#s: 

### 371691

Submission: 

### R31 0, New Products, RD Science Review

MRIDs: 

### Submitted: 47849601,47849602,47849603,47849604,47849605, 47849606

GLP: 

### No

MRID 47849601:

Title: 

### Efficacy ofa Water-Based Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: 

### OPPTS 8 I0.3300

Materials and Methods: 

### 2 experimental groups ofdogs, 6 dogs in each group, with weights ranging from 4.5-12.2 Ibs. One group was a treatment group and one was a control. Treated dogs were dosed with 1.5 mL ofa 55% etofenprox spot-on. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) 

### and 100 cat fleas (Cfelis). 

### Fleas were counted at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.
Study Summary ofthe Results:

### 1. Due to varying dog weights, the effective dose applied ranged between 150-407 mg/kg (mean of231 mg/kg). Dogs ranged in weight from 4.5-12.21bs. 2. Efficacy against fleas was only adequate through 16 days. 3. Efficacy against ticks was adequate through 31 days (mean efficacy of94%). 4. The dose applied is less than proposed on the label (2.0 mL for dogs 4-20 Ibs).

Entomologist's Observationsilliscussion:

1. While the data support efficacy claims on dogs for ticks through 30 days, the study is limited by the lack ofdogs at the upper margin ofthe weight class, which would be the most likely to have an inadequate level ofcoverage by a 2.0 mL application. 2. Because the rate applied is less than what is proposed on the product label, an approximation can be made based on the titration. For example, if 1.5 mL is adequate for

a 12 pound dog, then 2.0 mL would only be adequate for dogs up to 161bs (for ticks only). 3. Flea efficacy was not adequately supported by this study.

MRID 47849602:



### Title: Efficacy, at Minimum Dose Rate, of an Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: OPPTS 810.3300

Materials and Methods: 17 dogs were allocated to 3 treatment groups (5-6 dogs each). One

was an untreated control group, and the other groups were both treated with an etofenprox squeeze on, applied at 2 different dosages (2 mL and 4 mL, respectively). Dogs were grouped by size so that all dogs received an approximate dosage of250 mg/kg of etofenprox, as a minimum. Group B dogs were all approximately 7-10 Ibs, while Group C dogs were approximately 18-20 lbs. Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) and 100 cat fleas (C

### fe/is). Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.
Study Summary ofthe Results:

5. For Group B dogs receiving 2.0 mL oftreatment, flea and tick efficacy is adequate through 22 days after treatment. For Group C dogs receiving 4.0 

### mL oftreatment, efficacy is adequate through 29 days after treatment.
Entomologist's Observationsilliscussion:

1. While the study was designed to assess a 'minimum' dosage (250 mg etofenproxlkg animal), this meant that animals at the upper range ofthe the weight classification (i.e.,

### 20 lb dogs) received a treatment that is approximately double the dose instructed on the product label (2 mL product for dogs weighing 4-20 lbs). 2. Therefore, dogs in group C were treated with more material than what is on the proposed product label. The data from this study would only support efficacy claims for dogs under 10 lbs, which received 2 mL per animal, and those claims would only be valid for 22 days after treatment, not a full 30 days.



### MRID 47849603:



### Title: Efficacy, at Label Dose Volume and at Minimum Dose Rate, ofan Etofenprox Spot-on against Fleas and Ticks on Small Dogs

Guideline: OPPTS 810.3300



### Materials and Methods: 18 dogs were allocated to 3 treatment groups (6 dogs each). One was
an untreated control group, and the other groups were both treated with an etofenprox squeeze on, applied at 2 different dosages (2.5 mL and -4.5 mL, respectively). Dogs were grouped by size. Group B dogs were all approximately 8-9 lbs, while Group C dogs were approximately 18- 20 lbs. Group B dogs were treated with 2.5 mL ofspot-on per animal. Group C dogs were dosed by weight, so that each dog received 247 mg ai/kg, with applications thus varying from 4.3 mL to 4.7 mL per animal Infestations (and reinfestations over time) were conducted with 50 ticks (R. sanguineus) and 100 cat fleas (c.

### felis). Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % 

### Mortality was calculated in comparison to the control.



### Study Summary of the Results:

6. For Group B, flea efficacy was adequate through 16 days after treatment. 7. For Group B, tick efficacy was 89% for 23 days after treatment and 85% for 30 days after treatment. 8. For Group C, flea and tick efficacy was adequate through 30 days after treatment.


### Entomologist's ObservationslDiscussion:

1. Both treatment groups were treated with dosages exceeding that proposed on the submitted label, and thus the data are not valid to support efficacy claims for that proposed dosage. 2. For dosages applied as listed in the study, efficacy against fleas in Group B animals was only adequate through 16 days after treatment. Efficacy in Group C was maintained at 89% through 30 days after treatment. 3. For dosages applied as listed in the study, efficacy against ticks in Group B animals was demonstrated to be 89% at 23 days after treatment and 85% at 30 days after treatment. Efficacy in Group C was maintained through 30 days after treatment.

### MRID 47849604:



### Title: Evaluation of Sergeant's Etofenprox Squeeze-on Against Fleas, Ticks, and Mosquitoes on Dogs.

Guideline: OPPTS 810.3300

Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on, applied at 2.5 mL per animal. Dogs in the treatment group were all 10 Ibs or less, while control dogs ranged in weight from 11-14.3 Ibs. Infestations (and reinfestations over time) were conducted with 50 each of3 species ofticks (R. sanguineus, D. variabilis, andA. americana) at various infestation intervals, and 100 cat fleas (Cfelis). Fleas were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % 

### Mortality was calculated in comparison to the control. In the 3 rd 

### and 4th 

### weeks after treatment, all dogs were anesthetized and confined for 1 hour with 25 unfedAedes aegypti or (separately) with 25 Culex quinquefasciatus mosquitoes, inside a screen cage. Landings were counted for 5 minutes. Dogs were removed after I hour and mosquitoes were recovered to assess survival and blood feeding status.
Study Summary ofthe Results:

9. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 10. Flea efficacy was adequate through 23 days after treatment. 11. Tick efficacy was adequate through 16 days after treatment. 12. Treatment was not lethal to either species ofmosquitoes, but inhibited blood feeding >90% (compared to control) for 30 days for Aedes and 29 days for Culex.
Entomologist's Observationsilliscussion:

1. Dogs were treated with dosages exceeding that proposed on the submitted label, and thus the data are not valid to support efficacy claims for that proposed dosage. 2. For dosages applied as listed in the study (2.5 mL), efficacy against fleas is only supported for 23 days after treatment for dogs under 10 Ibs. 3. For dosages applied as listed in the study (2.5 mL), efficacy against ticks is only supported for 16 days after treatment for dogs under 10 lbs. 4. 

### For the 2.5 mL doses, claims against mosquitoes for prevention ofblood feeding are valid only for dogs less than 10 Ibs., and no kills claims are supported for mosquitoes.

MRID 47849605:

Title: 

### Efficacy of Sergeant's Etofenprox Squeeze-on against Ixodes scapularis Nymphs

### Guideline: OPPTS 810.3300



### Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on, applied at 2.5 mL per animal. Dogs in the treatment group were all 10 lbs or less, while control dogs ranged in weight from 11-14.3 lbs. 3 days after treatment, hair was clipped from each dog. Ten nymphal ticks placed in petri dishes with each hair sample and mortality was assessed at 24 h and 48 h after placement. % Mortality was calculated in comparison to the control.


### Study Summary ofthe Results:

13. Actual dosages applied to dogs ranged from 304-411 mg ai/kg. 14. Efficacy was 100% for ticks exposed to hair taken 3 days after treatment (100% mortality was observed at both 24 hand 48 h after placement on hair).



### Entomologist's Observationsilliscussion:

1. Distribution ofhair samples was not specified, and the randomization scheme was not defined (i.e., were mUltiple samples pooled for each dog, or were sub-replicates established for each dog?) 2. Because hair was clipped 3 days after treatment, claims against Deer ticks would only be valid for 3 days after treatment. This data would not support the one-month claim proposed on the label. A study that exposed ticks to hair taken 30 days after treatment would be required to demonstrate efficacy against deer ticks.



### MRID 47849606:

Title: Efficacy of a 2 mL Unit Dose of Sergeant's Etofenprox Squeeze-on, Applied at Minimum Dose Rates, against Fleas and Ticks on Small Dogs



### Materials and Methods: 12 dogs were allocated to 2 treatment groups (6 dogs each). One was
an untreated control group, and the other group was treated with an etofenprox squeeze on (55%), applied at 2.0 mL per animal (as proposed on new product label). Dogs in the treatment group were all 18-20 lbs., while control dogs ranged in weight from 20-30 lbs. Infestations (and reinfestations over time) were conducted with 50 each of 3 species ofticks 

### (R. sanguineus, D. variabilis, andA. americana) at various infestation intervals, and 100 cat fleas 

### (C./elis). Fleas

were counted via a comb at both 24 hours and 72 hours after each infestationlreinfestation. Ticks were counted by hand. Removal ofboth was done at 72 hours for mortality assessments. Weekly reinfestations were conducted until inadequate efficacy was shown. % Mortality was calculated in comparison to the control.


### Study Summary ofthe 

### Results:

15. Actual dosages applied to dogs ranged from 122-233 mg ailkg (mean 127 mglkg).

### 16. Flea efficacy was adequate through 16 days after treatment and 85% through 23 days after treatment. 17. Tick efficacy was adequate through 23 days after treatment and 80% through 30 days after treatment.

Entomologist's Observationsilliscussion:

I. This is the only study where the dosage applied to animals exactly matches the dosage on the proposed label, and also used dogs at the upper margin ofthe 20 Ibs. weight class. 2. Efficacy against fleas is only supported for 16 days after treatment and marginally for 23 days after treatment 3. Efficacy against ticks is only supported for 23 days after treatment.

Overall Review ofLabel Claims and Directions:

None ofthe studies were submitted under GLP standards, and protocols were vague on the exact specifications by which parasites were placed on animals (e.g., random anatomical distribution per 810.3300 guideline).

Claims against Deer Ticks, Ixodes, are not supported and must be removed from the label.

Claims against Mosquitoes are not supported for the application rate of2.0 mL proposed on the current label. The dosage would have to be raised to support this claim, and the claim must only be for repellence/suppression ofmosquito blood feeding. Kills and/or control claims are not supported by the data.

The preponderance ofdata indicates that a 2.0 mL application ofthe proposed 55% etofenprox product is not adequate to protect dogs on the upper end ofthe weight class for the 30 day retreatment interval from fleas and ticks. If animal safety data are adequate, the registrant should label the product for different application rates to different weight classes ofdogs. Some variability is evident even when the dosage is raised to 2.5 mL for small dogs under 10 Ibs. For dogs between 10-20 Ibs, the dosage should be raised to 4.5-5.0 mL in order to support the label claims of control offleas and ticks for 30 days.

Claims against flea eggs and larvae are not supported by this data and must be removed from the label. Also, claims regarding breakage ofthe flea life cycle and prevention offlea eggs from developing for up to 9 weeks (70 days) after application are not supported and also must be removed.

Removal ofunacceptable claims is deferred to the RM reviewer and PM, as some claims may possibly be acceptable under conditional registrations with later submission ofacceptable efficacy data.

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

February 26, 2010

MEMORANDUM OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES



### SUbject: Name ofPesticide Product: ETOFENPROXINYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES EPA Reg. No./File Symbol: 2517-RGG DP Barcode: DP 371681 Decision No.: 420097 Action Code: R310 PC Codes: 128965 (Etofenprox: 55%) 129032 (Pyriproxyfen: 2.2%)

From:

To: Byron T. 

### Backus, Ph.D., Toxicologist Technical Review Branch Registration Division (7505P)

Kevin Sweeney/Richard Gebken, RM 13 Insecticide Branch Registration Division (7505P)

# Or'-(S~ D 1.-/1.-10 (1.- 0 

### I 0 

# /I

# tJ--'4i**:J;;~<l**

Registrant: SERGEANT'S PET CARE PRODUCTS, INC.

FORMULATION FROM LABEL:

Active Ingredient(s): 128965 Etofenprox 129032 Pyriproxyfen Other Ingredient(s): TOTAL

ACTION REQUESTED: 

### The Risk Manager requests: Bywt. 55.00%

2.20% 42.80% 100.00%

"

...Please review the cited studies. Registrant claims they are similar to 69332-3."

Page I of3

### BACKGROUND:

The registrant is citing the acute toxicity studies in MRIDs 46161303 (acute oral LD 50), 46161304 (acute dermal LD50), 46161305 (eye irritation), 46161306 (dermal irritation) and 46161307 (dermal sensitization) to support the registration of2517-RGG. These studies were previously submitted for the formulation now registered as EPA Reg. No. 69332-3. In addition, the material received includes basic and alternate CSFs and proposed label for 2517-RGG.



### COMMENTS AND RECOMMENDATIONS:

I. After a comparison ofthe CSFs for 2517-RGG and for 69332-3, TRB concludes that the cited acute toxicity studies can be used as supporting data for 2517-RGG.

2. The cited studies have been previously reviewed and classified as acceptable (memorandum dated 10 February 2004 from R. Whiting ofTRB to Kevin Sweeney ofPM Team 13). The same memorandum accepted the registrant's waiver request for an acute inhalation toxicity study.

3. The acute toxicity study profile for EPA File Symbol 2517-RGG is as follows:

Acute oral toxicity IV Cited MRID 46161303 Acute dermal toxicity IV Cited MRID 46161304 Acute inhalation toxicity IV Waived Primary eye irritation III Cited MRID 46161305 Primary skin irritation IV Cited MRID 46161306 Dermal sensitization Negative Cited MRID 46161307

4. Based on the acute toxicity profile above, the following are the precautionary and first aid statements for 2517-RGG, as obtained from the Label Review System:

PRODUCT ID #: 002517-00133

PRODUCT NAME: ETOFENPROX/NYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES

PRECAUTIONARY STATEMENTS SIGNAL WORD: CAUTION

Hazards to Humans and Domestic Animals:

Causes moderate eye irritation. Avoid contact with eyes or clothing. [Wear protective eyewear.J* Wash thoroughly with soap and water after handling and before eating, drinking, chewing gu·m, or using tobacco.
*[Protective eyewear may be specified, if appropriateJ.

First Aid:

If in eyes: -Hold eye open and rinse slowly and gently with water for 15-20 minutes. -Remove contact lenses, if present, after the first 5 minutes, then continue rinsing. Page 2 00-Call a poison control center or doctor for treatment advice.

Have the product container or label with you when calling a poison control center or doctor or going for treatment. You may also contact 1-800-xxx-xxxx for emergency medical treatment information.

Page 300

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460

February 24, 2010

MEMORANDUM OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES



### Subject: Name ofPesticide Product: ETOFENPROX/NYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES EPA Reg. No./File Symbol: 2517-RGG DP Barcode: DP 371676 Decision No.: 420097 Action Code: R310 PC Codes: 128965 (Etofenprox: 55%) 129032 (Pyriproxyfen: 2.2%)

From: Byron T. Backus, Ph.D., Toxicologist Technical Review Branch Registration Division (7505P)

## n~(?_C 

# . o 1.-

- 1..- '"'"

- 1.- c l Co



### To: Kevin Sweeney/Richard Gebken, RM 13 Insecticide Branch Registration Division (7505P)
Registrant: SERGEANT'S PET CARE PRODUCTS, INC.

FORMULATION FROM LABEL:

Active Ingredient(s): 128965 Etofenprox 129032 Pyriproxyfen Other Ingredient(s): TOTAL

ACTION REQUESTED: 

### The Risk Manager requests:

"

...Please review the attached study and documentation."

Page 1 of 16

# .~

Bywt. 55.00%

2.20% 42.80% 100.00%

### BACKGROUND:

The material received includes a companion animal safety study (in MRID 47849609) titled: "Companion animal safety evaluation on dogs of spot-on products containing multiple toxicants and insect growth regulators" as well as a CSF and a proposed label for the product which would be applied to small and/or toy breed dogs weighing 4-20 Ibs. The label dosage rate is given as 2.0 mLidogiapplication.

COMMENTS AND RECOMMENDATIONS:

I. An 

### Agency contractor, Oak Ridge National Laboratory, conducted the primary review ofthe companion animal safety study. TRB performed the secondary review and made changes as necessary.

2. The study is not acceptable to support the proposed usees) on adult dogs and puppies and cannot be upgraded. Test groups consisted of6 (3 male and 3 female) adult dogs or puppies. The 870.7200 Companion Animal Safety Guidelines specify that at least 6 animals per sex should be used at each dosage level. In addition, the adult dogs that were treated with test substance II (containing 55.16% 

### w/w etofenprox, 8.78% 

### w/w methoprene, and 2.31% 

### w/w pyriproxyfen) at 5X the dosage rate weighed (on day -1) 4.06, 7.00, 7.98, 8.78, 8.94 and 9.10 kg. Since only one dog in this group weighed less than 91bs (4.06 kg = 

### 8.95 Ibs), the data could not be used to support the use ofthis formulation on adult dogs weighing 4-9 Ibs, particularly as the ratio ofbody surface area to mass could be a factor in absorption and toxicity. Cumulative dosage rates were 3.08, 3.21, 2.82, 2.56, 2.52 and 2.47 mLlkg (the 4.06 kg dog received a cumulative amount of 12.5 mL test material; the others each received 22.5 mL), with a mean of 2.78 mLlkg; dividing this by 5 (for the 5X margin ofexposure) gives 0.555 mLlkg, and dividing 2.0 mL (the proposed dose) by 0.555 mLlkg gives 3.60 kg (= 7.941bs), which is also substantially above the proposed 41b lower weight limit. For the puppies, it is impossible to compare and interpret differences in body weight gains between groups when there was such a range in ages (10-15 weeks, with no information as to specific ages for individual animals), the dogs were mixed breed and the two heaviest puppies (CC7 692 and CD4 7EC), which would be expected to show the greatest weight gains, were both in the control group.

3. TRB considers the behavioral changes (running and circling immediately after application of the test substance) in 7 animals (one adult, 6 puppies) as an adverse effect. It 

### is noted that the animals showing behavioral changes were all exposed to test material 

### IA (8.20% cyphenothrin, 9.8% fipronil, either in combination with material III, 8.90% methoprene and 2.43% pyriproxyfen, for the one adult, or in combination with material II, 55.16% etofenprox, 8.78% methoprene and 2.31 % pyriproxyfen for the puppies). Although the four puppies in group A2 (receiving 5 applications ofmaterial 

### IA and 5 ofII) showed running and circling only after the first application ofthe test substance and not after the second, third, fourth or fifth application, this may simply be an indication that the application area had been numbed.

4. Refer to the attached DER for additional comments.

Page 2 of 18DATA EVALUATION RECORD
CYPHENOTHRIN, FIPRONIL, ETOFENPROX, METHOPRENE, PYRIPROXIFEN COMPANION ANIMAL SAFETY STUDY- DOGSIPUPPIES

- (OPPTS 870.7200) MRID 47849609



### Primary Reviewer: Prepared for
Registration Division Office ofPesticide Programs U.S. Environmental Protection Agency One Potomac Yard 2777 S. Crystal Drive Arlington, V A 22202
Prepared by
Toxicology and Hazard Assessment Group Environmental Sciences Division

Oak Ridge National Laboratory Oak Ridge, TN 37831

Virginia A. 

### Dobozy, V.M.D

.. M.P.H. Signature: Date: Secondary Reviewers: Dana F. Glass, D.V.M. Signature: Date:

Robert H. Ross, M.S

.. Group Leader Signature: Date: Quality Assurance: Kimberly Slusher, M.S. Signature: Date:

Disclaimer



### This review may have been altered subsequent to the contractor's signatures above.

Oak Ridge National Laboratory managed and operated by UT_Battelle, LLC., for the U.S. Department of Energy under Contract No. DE_AC05_000R22725.EPA Reviewer: Byron T. Backns, Ph.D. Technical Review Branch, Registration Division (7505P) Signature:

# ()~. 

# n**~** Date: 0 1... -1.. 

### t - 1. C>**~** t> Template version 02/06 

# I DATAEVALUATIONRECORD

STUDY TYPE: Companion animal safety study· dogs/puppies

- OPPTS 870.7200

PC CODE: 128965· Ethofenprox, 129032· Pyriproxyfen, DP BARCODE: 371676

TEST MATERIAL (PURITy): Cyphenothrin (8.2% w/w), Fipronil (9.8% mlw), 

### Etofenprox (55.16% w/w), S-Methoprene (8.78% w/w), Methoprene (8.90% w/w) and Pyriproxifen (2.31% and 2.43% w/w)

TRADE NAME: Not provided

CITATION: Delport, P.C. (2009) Companion animal safety evaluation on dogs of spot-on products containing multiple toxicants and insect growth regulators. ClinVet International (Pty) Ltd., Bloemfontein, Republic of South Africa. Study No. CV 08/551, August 6,2009. MRID 47849609. Unpublished.

SPONSOR: Sergeant's Pet Care Products, Plano, Texas

EXECUTIVE SUMMARY: In a companion animal safety study (MRID 47849609), groups of random-source adult (> 

### 6 months of age) and juvenile (10-15 weeks ofage) dogs were topically administered 3 combinations ofinsecticides and insect growth regulators or one inert substance. Two groups ofthree male and three femalejuvenile dogs were administered test substance IA (8.2% w/w cyphenothrin and 9.8% m/w fipronil; Batch No. 012003-09) and test substance II (55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w pyriproxifen; Batch No. 011901-09) at either IX (recommended dose) or 5X (recommended dose hourly for 5 applications). The test substances were applied simultaneously as adjacent stripes along the dorsum ofthe dog from behind the ears caudally to the base ofthe tail. Two groups ofthree male and three female adult dogs weighing 9-20 kg were administered the test substance IA and test substance III (8.90% w/w methoprene and 2.43% w/w pyriproxifen; Batch No. 011902-09) at either IX (recommended dose) or 5X (recommended dose hourly for 5 applications). The test substances were applied as previously described. A group ofthree male and three female adult dogs weighing less than 9 kg was administered test substance II at 5X (recommended dose hourly for 5 applications). A group ofthree male and three femalejuvenile dogs and another group ofthree male and three female adult dogs were administered control substance IVA (Batch No. 012004-09) containing inert ingredients (not otherwise stated) at 5X the recommended dose. The groups and test materials they received are shown in the table below:

Page4ofl8Group A Group AI (n-6) Puppies (10-15 weeks) Group A2 (0-6) Puppies (10-15 weeks) Single application ofsubstance IA Five applications ofsubstance IA Single application ofsubstance II Five applications ofsubstance II

B Group B I (0 6) Adults (9-20 kg) Group B2 (n 6) Adults (9-20 kg) Group B3 (0 6) Adults «9 kg) Single application ofsubstance IA Five applications ofsubstance IA Five applications ofsubstance II Single application ofsubstance III Five applications of substance III C Group CI (0-6) Puppies (10-15 weeks) Group C2 (0-6) Adults (9-20 kg) Five <ipplications control substance IVA Five applications control ofsubstance IVA

0 0 Substance IA contams 8.2 Yo **w/w** cyphenothnn and 9.8 Yo m/w fiproOlL Substance II contains 55.16% **w/w** etofenprox, 8.78% **w/w** s-methoprene, 2.3 1% **w/w** pyriproxifen. Substance III contains 8.90% methoprene, 2.43% **w/w** pyriproxifen. Control substance IVA contains inert control substances.



### The animals were observed for clinical signs oftoxicity and dermal irritation for four hours postapplication and then twice daily for the duration ofthe study (14 days post-application). Body weight, body weight gain, food consumption and clinical pathology parameters (hematology and clinical chemistry) were measured at the required intervals.

All animals survived to the end ofthe study. Immediately after treatment, one adult dog in Group BI (IX applications oftest substances IA and III) showed behavioral changes (running, circling). This behavioral change was not considered treatment-related in adults by the sponsor since it was not observed at 5X the recommended dose. Immediately after treatment, two puppies in Group Al (IX application oftest substances IA and II) showed behavioral changes (running, circling). Four puppies in Group A2 (5X application oftest substances IA and II) showed similar behavioral changes after the first application but not after subsequent applications. These behavioral changes are considered to be an adverse effect. White crystallization was observed on the hair tips ofmany adult and juvenile dogs in the treated and control groups. The application sites ofall dogs in Group B3 (5X application oftest substance II) had an oily or wet appearance. The sign disappeared from one dog on Day 

### + 14 but was present on all others at the end ofthe study.

All adult dogs and puppies gained weight from Day -I to Day 14. However, mean weight gain in pups 

### in the treated groups (A I and A2) was 15% lower than the control group pups. The mean weight gain in the treated adult animals (Groups BI, B2 and B3) was decreased (30-99% as compared to the control group). The difference relative to controls was largest in the smaller adult dogs in Group B3 (99% decrease as compared to the control group). Food consumption

was not affected by treatment. No treatment-related hematology or clinical chemistry changes
were observed.

It 

### is noted that the 7 animals (one adult, 6 puppies) that showed behavioral changes (running and circling) immediately after application ofthe test substance were all exposed to test material IA (8.20% cyphenothrin, 9.8% fipronil, either in combination with material III, 

### 8.90% methoprene and 2.43% pyriproxyfen, for the one adult, or in combination with material 

### II, 55.16% etofenprox, 8.78% methoprene and 2.31 % pyriproxyfen for the puppies). Although the four puppies in group A2 (receiving 5 applications ofmaterial IA and 5 ofII) showed running and circling only after the first application ofthe test substance and not after the second, third, fourth

or fifth application, this may simply be an indication that the application area had been numbed.

Page 5 of 18

### Test groups consisted of 6 (3 male and 3 female) adult dogs or puppies. The 870.7200 Companion Animal Safety Guidelines specify that at least 6 animals per sex should be used at each dosage level. In 

### addition, the adult dogs that were treated with test substance II (containing 55.16% w/w etofenprox, 8.78% w/w methoprene, and 2.31 % w/w pyriproxyfen) at 5X the dosage rate weighed (on day -1) 4.06, 7.00, 7.98, 8.78, 8.94 and 9.10 kg. Since only one dog in this group weighed less than 9lbs (4.06 kg = 

### 8.95 lbs), the data could not be used to support the use of this product/formulation on adult dogs weighing 4-9 lbs, particularly as the ratio of body surface area to mass could be a factor in absorption and toxicity. Also, it was not possible to compare body weight changes between adult group B3 (which received the etofenprox-containing formulation) and the control (C2) group because initial mean body weights were so different. For the puppies, it is impossible to compare and interpret differences in body weight gains between groups when there was such a range in ages (10-15 weeks, with no information as to specific ages for individual animals), the dogs were mixed breed and the two heaviest puppies (CC7 692 and CD4 7EC), which would be expected to show the greatest weight gains, were both in the control group.

In 

### addition, it is concluded that the margin of safety in puppies administered simultaneous topical application of test substances IA (8.2% w/w cyphenothrin and 9.8% m/w fipronil) and II (55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31% w/w pyriproxifen)

was less than IX the recommended dose, based on clinical signs of toxicity (behavioral changes immediately post-application).

This companion animal safety study in male and female random-source adult dogs and puppies is Unacceptable/Guideline and does not satisfy the guideline requirement for a companion animal safety study (OPPTS 870.7200) in the dog and cannot be upgraded for either adults or puppies. See Study Deficiencies section for details. Major deficiencies include too few animals per group, failure to test the end-use product and lack ofsome required reporting.

COMPLIANCE: Signed and dated GLP, Quality Assurance and Data Confidentiality statements were provided for Clin Vet International. Pathcare Veterinary Laboratory, which conducted the hematology and clinical chemistry analyses, is not GLP accredited but is ISO 15189 certified.

Page 6 of 18

### I. MATERIALS AND METHODS

A. MATERIALS:

1. Test materials:

la. Test substance 1 (code uame IA) Description:
Batch #: Purity: Storage: Compound Stability:
CAS#: Not provided
012003-09 8.2% w/w cyphenothrin and 9.8% mlw fipronil*
At room temperature Expiration date: January 20, 2011
Not provided 

### * Batch 2008-Fip.D3, expiration date August 19, 2010, packed in foil and stored at ambient temperature, inside carton box, dry

lb. Test substance 2 (code name II) Description:
Batch #: Purity: Storage: Compound Stability:
CAS#: Not provided
011901-09 55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31 % w/w pyriproxifen
At room temperature Expiration date: January 19, 2011
Not provided

Ie. Test substance 3 (code name ITI) Description:
Batch #: Purity: Storage: Compound Stability:
CAS#: Not provided
011902-09 8.90% w/w methoprene, 2.43% w/w pyriproxifen
At room**t~mperature** Expiration date: January 19, 20ll
Not provided

ld. Control substance (code name IVA) Description:
Batch #: Purity: Storage: Compound Stability:
CAS#: Not provided
012004-09
Inert control substance (no purity provided)
At room temperature Expiration date: January 20,2011
Not provided

2. Vehicle control: See control substance described in Id. above.

Page 7 of 18

### 3. Test animals: Species: Strain: Age/weight

Source: Housing: Diet:

Water:
Environmental conditions: Temperature: Humidity: Air changes: Photoperiod: Acclimation period:

B. STUDY DESIGN: Dog Described as "indifferent" Groups Al and A2: 10-15 weeks on day 0 (2.12 -7.32 kg or 4.67-16.14Ibs) Groups B I and B2: 2: 6 mos on day 0 (> 9 kg 0" 20 kg or > 19:84 lb 

### :s 44.09Ibs) Group B3: 2: 6 mos on day 0 (0" 9 kg or 0" 19.84Ib) Group CI: 10-15 weeks on day 0 (2.88

- 9.67 kg or 6.35-2I.32Ibs) Group C2: 2: 6 mos on day 0 (> 9 kg 

### :s 20 kg or > 19.84 lb 

### :s 44.09 lbs) ClinVet International (Pty) Ltd. Colony Individually housed in pens Adults (>12 months) were fed a commercial dry dog food (example: ULTRADOG SUPERWOOF DOG FOOD); puppies « 12 months) were fed an "appropriate puppy food" (example: Eukanuba puppy and junior medium breed) Tap water, ad libitum

20 ± 4" C Not provided 12-15 air changes/hr 12 hours light/12 hours dark Fourteen days

1. In life 

### dates: Start: March 19, 2009; End: April 16, 2009

2. Animal 

### assignment: Forty-two animals were assigned to the study. The genders were separated and the dogs allocated to study groups (Table I) within the body weight requirements using randomization through minimization with body weight as the only criterion. For medium sized adult dogs, within each gender, animals were blocked into three blocks ofthree dogs each. The three heaviest dogs formed block I; the next three heaviest dogs formed block 2 and the next three formed block 3. Within blocks, dogs were allocated to one ofthree groups, I, 2 or 3. The first animal ofblock I was assigned to group I, the second to group 2 and the third to group 3. The first animal ofblock 2 was assigned to group 3, the second to group 2 and the third to group I. The first animal ofblock 3 was assigned to group 1, the second to group 2 and the third to group 3. Groups 1,2 and 3 were then randomly assigned to the actual groups BI, B2 and C using Excel randbetween. Puppies

were similarly assigned to groups AI, A2 and Cl. The six dogs in group B3 were allocated;

no randomization was possible.

Page 8 of 18Table 1: Study design Groul'

A Group AI (n 6) Puppies (l0-15 weeks) Group A2 (n 6) Puppies (l0-I5 weeks) Single application of substance lA Five applications ofsubstance IA Single application of substance II Five applications of substance II

B Group B I (n-6) Adults (9-20 kg) Group B2 (n-6) Adults (9-20 kg) Group B3 (n-6) Adults «9 kg) Single application of substance IA Five applications of substance lA Five applications ofsubstance II Single application ofsubstance III Five applications of substance III C Group CI (n-6) Puppies (l0-I5 weeks) Group C2 (n-6) Adults (9-20 kg) Five applications control substance IVA Five applications control of substance IVA Substance IA contams 8.2% w/w cyphenothrm and 9.8% m/w fiproml. Substance II contains 55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31% w/w pyriproxifen. Substance III contains 8.90% methoprene, 2.43% w/w pyriproxifen. Control substance IVA contains inert control substances.


### 3. Dose selection rationale: The dose rates for test substance IA are based on fipronil and methoprene on the Frontline Plus label and pyriproxyfen in Sergeant's Gold for Dogs. For test substance II, the study report states that the maximum etofenprox small dog dose rate is 758 mg/kg. For test substance III, the dose ofpyriproxyfen and s-methoprene is based on Sergeant's Gold for Dogs and Frontline Plus label. However, none ofthe dose rates used is representative ofthe proposed label.

4. Preparation and treatment: The test and control substances were applied as measured doses from syringes (without needles) to a furrow in the hair on the back, starting high on the neck behind the ears and extending caudally towards the base ofthe tail. The fur was not shaved or clipped. Technicians applying the substances were blinded to the test material. Test substances lA, II and III were applied separately as "terminally adjacent stripes, applying test substance IA anterior to test substance II or test substance IA anterior to test substance III." The placebo control fonnulation IVA was applied separately. Substances lA, II and III were not mixed.

Test substances IA and II were applied as single doses, once only, to the pups in test group Al and five times consequently at hourly intervals, each time as a single dose, to the pups in test group A2. Substances IA and II were not mixed.

Test substances IA and III were applied as single doses, once only, to the adult dogs in group BI, five times consequently at hourly intervals, each time as a single dose, to the adult dogs in group B2. Substances IA and III were not mixed. Test substance II was applied five times consequently at hourly intervals, each time as a single dose, to the adult dogs in group B3.

The control substance IVA was applied five times consequently at hourly intervals, each time
as a single dose, to pups and dogs in groups CI and C2, respectively.

The dose volumes ofthe test and control substances were detennined by the animal's weight
on Day -1 (Table 2).

Page 9 of ISTable 2: Doses Group Test substance Total dose administered Al (puppies) IA 0.83

- 2.0 mL (IX) II 3.1 -7.5 mL (IX) A2 (puppies) IA 5.0

- 13.30 mL (1.0

- 2.66 mL x 5) II 18.8

- 50.0 mL (3.76

- 10.0 mL x 5) BI (adults) IA 1.34 mL (IX) III 1.34 mL (IX) B2 (adults) IA 3.4

- 6.7 mL (0.68

- 1.34 mL x 5) III 3.4

- 6.7 mL (0.68 -1.34 mL x 5) B3 (adults) II 12.5

- 22.5 mL (2.5

- 4.5 mL x 5) CI (puppies) IVA 13.10 mL (2.62 mL x 5) C2 (adults) IVA 5.0 mL (1.0 mL x 5) Substance IA contams 8.2% w/w cyphenothnn and 9.8% m1w fiproml. Substance II contains 55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31% w/w pyriproxifen. Substance III contains 8.90% methoprene, 2.43% w/w pyriproxifen. Control substance IVA contains inert control substances.


### S. Statistics: The emphasis ofthe statistical analyses was the change from baseline ofeach of the hematology and clinical chemistry parameters. Individual hematology and clinical chemistry values on test days were tabulated separately for each variable and each group, together with the following descriptive statistics: mean, standard deviation (SD), coefficient ofvariation (CV %), 

### geometric mean, geometric SD, minimum, maximum and the number of observations in the group. The individual changes and percentage changes from baseline (test day -3) for each ofthe post-treatment days were calculated and tabulated for each variable and each group. The number ofpost-treatment values that fell outside the reference range
was calculated. The post-treatment values were compared to the baseline values in an intratreatment comparison by means ofan analysis ofvariance (ANOVA) with an animal and observation time as effects. An inter-treatment comparison with respect to the changes from baseline was also performed. The post-treatment values ofeach the three test treatment groups (BI, B2 and B3) were compared to the control group (C2) for adult dogs. The posttreatment values of each ofthe two test treatment groups (AI and A2) were compared to the two control groups (CI) for puppies. An analysis ofcovariance (CO-ANOVA) with a treatment effect and the baseline values as covariate was used for the analyses. In addition, the change from baseline values ofeach ofthe three treatment groups (BI, B2 and B3) were compared to those ofthe control group (C2) for dogs and the two test groups (AI and A2)

were compared to those ofthe control group (CI) for puppies by means of an ANOVA with

a treatment effect. Groups Al and A2 were compared in a similar way.


### C. METHODS:



### 1. Observations:

a. General health observations: The animals were observed daily for general health. Specific health observations were observed hourly on the day ofapplication until four hours after application ofthe test material and twice daily, thereafter, for the duration of the study. Observations included, but were not limited to, changes in skin and fur, eyes and mucous membranes, nervous signs and behavior pattern as well as vomiting and diarrhea. Local tolerance observations were also included. Page 10 of 18

### b. Veterinary examinations: Physical examinations were conducted by a veterinarian on Days -14, -3, +1, +7 and +14. The examinations included but were not limited to body temperature, pulse rate, auscultation ofthe heart and lungs, mucous membranes and skin, joints, eyes, ears, mouth and genital organs.



### 2. Body weight: Animals were weighed on Days -14, -7, -1, +1, 

### +7 and + 14.



### 3. Food consumption: The amount offood offered was measured and the food consumption

was recorded daily and scored using the following scoring system.

Fc 1 - 0- 25% Fc 2 - >25- 50% Fc 3 - >50-75% Fc 4 - >75-100%



### 4. Hematology and clinical chemistry: Blood was collected from thejugular vein for hematology and clinical chemistry assessments on fasted animals on the following days:

- 3, +1, +7 and +14. The tests were conducted by Pathcare, Bloemfontein, South Africa, because ClinVet International did not have the expertise and apparatus to perform the analyses. The CHECKED (X) parameters were examined.



### a. Hematology

X Hematocrit (HCT)' X Leukocyte differential count* X Hemoglobin (HOB), X Mean corpuscular HOB (MCH)* X Leukocyte count (WBC)' X Mean corpusc. HOB conc.(MCHC)* X Erythrocyte count (REC)' X Mean corpusc. volume (MCV)* X Platelet count* X Reticulocyte count Blood clotting measurements* X (Thromboplastin time) (Fibrinogen) X (Prothrombin time) *Recommended for companIon anImals safety evaluatIOn based on OPPIS 870.7200

Page 11 of IS

### b. Clinical chemistry

ELECTROLYTES OTHER X Calcium

### * X Albumin* X Chloride* X Creatinine* Magnesium X Urea nitrogen* X Phosphorus 

### * Total Cholesterol X Potassium' (K) X Globulins* X Sodium' (NA) X Glucose* ENZYMES (more than 2 hepatic enzymes, eg., *) X Total bilirubin 

### *
X Alkaline phosphatase (AP)' X Total protein* Cholinesterase (ChE) Triglycerides Creatine kinase Albumin/Globulin ratio Lactic acid dehydrogenase (LDH) X Direct bilirubin* X Alanine aminotransferase (ALT/also SGPT)* Indirect bilirubin X Aspartate aminotransferase CAST/also SGOT)* BUN/Creatinine ratio Gamma glutamyl transferase (GGT) Te02 Bicarbonate Amylase Sorbitol dehydrogenase 

### * Recommended for a compamon animal safety evaluatIOn based on OPPTS 870.7200



### 5. Urinalysis: Urinalysis was not conducted.

6. Sacrifice and pathology: The study did not have a scheduled necropsy.

II. RESULTS

A. 

### ACTUAL DOSES ADMINISTERED: The mg/kg doses ofactive ingredients were not calculated. Based on calculations by tbe EPA reviewer, the mLlkg doses to puppies were significantly higher than those to adults. For example, adults in Group Bl weighing 1l.3 to 19.38 kg received 1.34 mL each oftest substances IA and III for a 0.12 to 0.07 mLlkg dose ofeach substance. Puppies in Group AI weighing 2.12 to 5.56 kg received 0.83 to 2.0 mL of test substance IA for a 0.36 to 0.39 mLlkg dose, approximately 5 times the adult dose. Puppies in Group IA received 3.1 to 7.5 mL oftest substance II 

### for a l.34 to l.46 mLlkg dose, approximately 19 times the adult dog dose.

B. 

### OBSERVATIONS:

1. Clinical signs of toxicity: Immediately after treatment, one adult dog in Group B 1 showed behavioral changes (running, circling). Another adult dog in Group B3 had skin irritation on tbe shaved area ofthe neck (assumed to be area shaved for blood collection). In Group C2,

one dog had loose feces three hours post-application, one dog had loose mucoid feces with blood on Day +2 and another dog had mucoid feces on Day +2. Minor clinical signs observed in adult dogs after treatment included the following: swollen mammary gland (Group C2, Days +7 and +14); scab on scrotum (Group C2, Day +14); eczema on neck (Group B3, Day +7); hair loss on chin (Group B3, Days +7 and +14); and right eye lacrimation (Group B2, Day +7). A female in Group B I came into estrus on Day + 1.

Page 12 ofl8

### Immediately after treatment, two puppies in Group Al showed behavioral changes (running, circling). Four puppies in Group A2 showed similar behavioral changes after the first application but not after subsequent applications. One pup in Group Al had loose feces on Day + 1 with blood on Day +4. A pup in Group A2 had loose feces on Day + 13. Minor clinical signs in puppies after treatment included the following: thinning ofhair in one pup in Group A2 on Day +7 which was diagnosed as demodicosis on Day +14; thinning ofhair (Group A2, Day +14); and scales (two pups in Group CI, Day +14). While the demodicosis (mange) was not life threatening, its occurrence suggests that the overall health ofthe dogs and puppies may have been compromised.

2. Application site examination: White crystallization was observed on the hair tips ofadult dogs in Groups B 1 [four dogs at one hour post-application and one dog on Day + 1], B2 (three dogs at one hour post-application, one dog on Day +1 

### and two dogs on day +2), B3 (two dogs at one hour post-application, four dogs at three hours post-application and one dog at Day +2) and C2 (three dogs at two hours post-application, one dog at 3 hours postapplication, one dog at four hours post-application and one dog at Day +2). The application sites ofall dogs in Group B3 had an oily or wet appearance. The sign disappeared from one dog on Day + 14 but was present on all other dogs at the end ofthe study.

White crystals were observed on the hair tips ofpups in Groups Al (two pups at one hour post-application and one pup at three hours post-application), A2 (one pup each at one hour and two hours post-application) and Cl (three pups at one hour post-application and one pup at two hours post-application).

3. Mortality: All adult andjuvenile dogs survived to the end ofthe study.

B. 

### BODY WEIGHT AND WEIGHT GAIN: Body weight data are presented in Table 3. All adult andjuvenile dogs gained weight from Day -1 to Day 14. However, mean weight gain in pups in the treated groups (AI and A2) was 15% lower than the control group pups. The

mean weight gain in the treated adult animals was decreased (30-99% as compared to the control group). The change was largest in the smaller adult dogs in Group B3 (99% decrease

as compared to the control group).

Page 13 of 18Table 3: Mean body weight and body weight gain' Body weight (kg) Group Day-I Day +I b Day +7 b Day +14 Al (puPs) 4.24 4.30 4.78 5.44 A2 (pups) 4.94 5.06 5.54 6.15 Cl (pups) 5.24 5.50 5.89 6.66 Bl (adults) 16.Q7 16.41 16.63 16.62 B2 (adults) 15.56 15.48 15.75 15.80 B3 (adults) 7.64 7.62 7.62 7.65 C2 (adults) 16.05 16.30 16.93 16.84
a N = 6/group, except where noted.

b Calculated by the reviewer from data on pages 46-47, MRlD 47849609

C Decrease compared to control group, calculated by the reviewer Body weight gain Day-I to+l b Day -I to +7' 0.06 0.54 0.12 0.60 0.26 0.65 0.34 0.56 -0.08 0.19 -0.02 -0.02 0.25 0.88 kg)Day -I to +14 1.20 (15%)' 1.21 (15%)' 1.42 0.55 (30%)' 0.24 (70%)' 0.01 (99%)' 0.79

Group Al treated at IX with Substance IA (8.2% w/w cyphenothrin and 9.8% rn/w fipronil) and Substance II (55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.31 % w/w pyriproxifen) Group A2 treated at 5X with Substance IA (8.2% w/w cyphenothrin and 9.8% mlw fipronil) and Substance II (55.16% w/w etofenprox, 8.78% w/w s-methoprene, 2.3 1% w/w pyriproxifen) Groups CI and C2 treated at 5X with Control substance IVA Group B I treated at IX with Substance IA (8.2% w/w cyphenothrin and 9.8% rn/w fipronil) and Substance III (8.90% methoprene, 2.43% w/w pyriproxifen) Group B2 treated at 5X with Substance IA (8.2% w/w cyphenothrin and 9.8% rnIw fipronil) and Substance III (8.90% methoprene, 2.43% w/w pyriproxifen)



### C. FOOD CONSUMPTION: No treatment-related effects were reported.

D. CLINICAL PATHOLOGY ANALYSES:

L Hematology: No treatment-related changes were observed in adults or pups. An 

### increase (as compared to the control group) in monocyte counts in Group Bl adult dogs on Day 

### +I was not considered toxicologically significant.

2. Clinical Chemistry: No treatment-related effects were reported in adults or pups. A decrease (as compared to the control group) in creatinine in Group B3 on Day +7 and a decrease in AST in Group B3 on Day 

### +14 were not considered toxicologically significant. The mean glucose value in Group A2 was increased from baseline (Day -3) to Days +1 

### and +14. The mean chloride values in Groups Al and A2 were increased from baseline to Day +7. These deviations are not considered toxicologically significant.

III 

### DISCUSSION AND CONCLUSIONS

A. INVESTIGATORS' CONCLUSIONS: The study author concluded that two test substances, blend IA containing 8.20% w/w cyphenotillin and 9.80% 

### mlw fipronil and blend II containing 55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w pyriproxifen, were safe to use under the conditions ofthe study when applied simultaneously

as a spot-on to puppies at the recommended dose as well as five times (5X) the recommended dose.

Blend II containing 55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31% w/w pyriproxifen, was safe to use under the conditions ofthe study when applied topically to adult dogs at five times the recommended dose. Page 14 ofI8

### Two test substances, blend IA containing 8.20% 

### w/w cyphenothrin and 10.07% 

### w/w fipronil and blend III containing 8.90% 

### w/w methoprene and 2.43% 

### w/w pyriproxifen, were safe to
use under the conditions ofthe study when applied simultaneously as a spot-on to adult dogs at the recommended dose as well as at five times the recommended dose.

B. REVIEWER COMMENTS: All animals survived to the end ofthe study. Immediately after treatment, one adult dog in Group B1 (IX applications oftest substances IA and III) showed behavioral changes (running, circling). Immediately after treatment, two puppies in Group Al (IX application oftest substances IA and II) showed similar behavior. Four puppies in Group A2 (5X application oftest substances IA and II) showed the same behavior after the first application but not after subsequent applications. The behavioral signs are considered treatment-related in puppies since they occurred in multiple animals both at IX and 5X the recommended dose. The behavioral change in adult dogs is considered treatment-related since it also occurred in puppies.

White crystallization was observed on the hair tips ofmany adult and puppies in the treated and control groups. The application sites ofall dogs in Group B3 (5X application oftest substance II) had an oily or wet appearance. The sign disappeared from one dog on Day + 14 but was present on all other dogs at the end ofthe study. Since there was no skin irritation, the signs are considered cosmetic. However, the persistence oftest substance II on the hair of dogs for more than 14 days is ofconcern due to potential human exposure of owners to pets.

All adult andjuvenile dogs gained weight from Day -1 to Day 14. However, mean weight gain in pups in the treated groups (AI and A2) was 15% lower than the control group pups. The change is considered treatment-related. The mean weight gain in the treated adult animals (Groups B1, B2 and B3) was decreased (30-99% as compared to the control group). The change was largest in the smaller adult dogs in Group B3 (99% decrease as compared to the control group). The animals were considered adults ifthey were >6 months ofage. Adult dogs usually are not expected to change weight in a 14-day period; however, dogs as young
as 6 months may still be gaining weight. The birth dates ofthe animals were not provided so their exact age is unknown. Since the decreases from the control group were large, the decreased body weight gain is considered treatment-related in adults. Food consumption was not affected by treatment. No treatment-related hematology or clinical chemistry changes

were observed.

It 

### is concluded that the margin of safety in 

### puppies administered simultaneous topical applications oftest substances IA (8.2% 

### w/w cyphenothrin and 9.8% 

### m/w fiproniI) and II (55.16% 

### w/w etofenprox, 8.78% 

### w/w s-methoprene and 2.31 % 

### w/w pyriproxifen) was less than IX the recommended dose, based on clinical signs of toxicity (behavioral changes immediately post-application).

It 

### is concluded that the margin of safety in 

### adult dogs (9-20 kg) administered simultaneous topical application of test substances IA (8.2% 

### w/w cyphenothrin and 

### 9.8% m/w fipronil) and III 

### (8.90% 

### w/w and 2.43% 

### w/w pyriproxifen) was less than IX the recommended dose, based on clinical signs oftoxicity (circling and running in 

### one dog after application).
Page 15 of 18It is concluded that no margin of safety in adult dogs 

## « 9 kg) administered a topical application of test substance II (55.16% w/w etofenprox, 8.78% w/w s-methoprene and 2.31 % w/w pyriproxifen) could be established from the findings ofthis study.

This study is unacceptable and cannot be upgraded for either adult dogs or puppies.



### C. STUDY DEFICIENCIES:

a. The study report states that the purpose ofthe study is to detennine the safety ofa combination ofthree test formulation spot-on products containing three toxicants and two insect growth regulators. The Companion Animal Safety Guideline (OPPTS 870.2700) requires that a study be conducted with the end-use product using the label dose and directions for use, although there is a provision for use ofa max/tox product containing multiple toxicants at the maximum levels which would be anticipated in fonnulated topical products. However, this does not appear to have been the objective ofthe study. It is also unclear why different combinations ofproducts were tested in adult andjuvenile animals. Pups were administered test substances IA and II, whereas large adult dogs were administered test substances IA and III and smaller dogs were administered test substance II alone.

b. Other Companion Animal Safety Guideline non-compliances are as follows:

I. The study used three dogs/sex/group, whereas six dogs/sex/group are required. 2. Individual animal data for clinical signs were not provided. 3. Group mean values for body weight were not calculated for Days -14, -7, + 1 and +7. 4. The control formulation is described as "inert control substance". However, it is not certain for which ofthe test formulations was this the "inert control substance," as no analysis was provided. 5. The date ofbirth ofthe animals was not provided. 6. The mg/kg dose ofactive ingredients was not calculated. 7. The laboratory which conducted the hematology and clinical chemistry testing is not GLP accredited. 8. The Guideline allows for five hourly applications ofa IX dose to achieve the 5X dose. However, with the large volumes oftest material used on some ofthe smaller animals, it is likely that the material ran off and was not available for absorption. 9. The study report states that test substances lA, II and III were applied separately as tenninally adjacent stripes, applying test substance IA anterior to test substance II or test substance IA anterior to test substance III. It is unclear how the second substance could be applied anteriorly when both were administered from the neck to the base of the tail. 10. A certificate ofanalysis was not provided for each ofthe test substances. The study report states that the concentration ofcyphenothrin in test substance IA should have been 15% as stated in the protocol but a certificate ofanalysis indicated that it was 8.2%.

Page 16 of 1811. The study author's conclusion (page 56) gives different percentages of fipronil in test substance IA when discussing the findings 

### in puppies (9.8% m/w) and adults (10.07% w/w).

Page 17 of 181. DP 

### BARCODE: 371676 2. PC CODES: 128965 (Etofenprox); 129032 (Pyriproxyfen) 3. CURRENT DATE: February 24, 2010 4. TEST MATERIALS: Blend IA: 8.20% 

### w/w cyphenothrin, 9.80% 

### w/w fipronil; Blend II: 55.16% 

### w/w etofenprox, 8.78% 

### w/w methoprene, 2.31 % 

### w/w pyriproxyfen; Blend III: 8.90% 

### w/w methoprene, 2.43% 

### w/w pyriproxyfen; Blend IVA: inert control substance

Study/Species/Lab MRID Results Tox. Core

Study # / Date Cat. Grade Companion Animal Safety Study/Dogs & 47849609 Four groups (each 6M & 6F) of N/A U Puppies adult dogs; 3 groups (each 6M & 6F) ofpuppies were used. Adults: ClinVet International (Pty) Ltd; Group B I IX IA&III; Group B2: Bloemfontein, South Africa 5X IA&II1, Group B3: 5X II; Group C2 5X IVA. Puppies: Study CV 08/551 I August 6, 2009. Group AI IX IA&II; Group A2: 5X IA&II; Group C I: 5X IVA. Not possible to adequately interpret data from design of study.

Core Grade Key. A - Acceptable, S - Supplementary, U - Unacceptable, W - WaIved

Page 18 of 18UNITE" hATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460



### September IS, 2009



### SERGEANT'S PET CARE PRODUCTS, INC. SERGEANT'S PET CARE PRODUCTS, INC. 262S 

### SOUTH IS8TH PLAZA OMAHA, NE 68130-1703

Report ofAnalysis for Compliance with PR Notice 

### 86-S OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES



### Thank you for your submittal of 1 0-SEP-09. Our staffhas completed a preliminary analysis ofthe material. The results are provided as follows:

Your submittal was found to be in full compliance with the standards for submission of data contained in PR Notice 

### 86-S. A copy ofyour bibliography is enclosed, annotated with Master Record ID's (MRIDs) assigned to each document submitted. Please use these numbers in all future references to these documents. Thank you for your cooperation. Ifyou have any questions concerning this data submission, please raise them with the cognizant Product Manager, to whom the data have been released.

### September 10, 2009

Richard Gebken Product Manager 10 Document Processing Desk (REGFEE) Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
SUbject: Submission ofa Section 3 Registration Application EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies

Dear Mr. 

### Gebken: Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 20036

telephone 202-772-4900 facsimile 202-772-4979 www.exponent.com



### On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158'h Plaza, Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies. Please find enclosed the following support documents:

• Transmittal document;

• EPA 8570-1;

• EPA 8570-27;

• Confidential Statement ofFormula (three copies);

• EPA 8570-34;

• Data Matrix;

• Draft Label (five copies); and

• Copy ofPRIA paperwork for 50% waiver/reduction and payment check.

As discussed with EPA during a meeting on August 19, 2009, Sergeant's is submitting EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332- 3). The product has been formulated and labeled for application to dogs and puppies 4-20 pounds.

The enclosed application for registration is for a new end-use product (substantially-similar formulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review ofdata package within RD, PRIA review time frame 6 months, and

a fee of$4,578. Sergeant's qualifies for a PRIA fee waiver/reduction of50% (refer to OPP Decision Number D-408042).

### Ifyou have any questions, please contact me at 202-772-4932.

# ~~r;t 

# ' '. t[jL--·

# ;7Js~. Messina

1,uthorized Representative of

Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kimberly Nesci, EPA Bob Scharf, Sergeant's Kelly Hoskins, Sergeant's Larry Nouvel, Nouvel Rick Tinsworth, Exponent

### September 10, 2009

Richard Gebken Product Manager 10 Document Processing Desk (REGFEE) Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
Subject: Submission ofa Section 3 Registration Application EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies

Dear Mr. Gebken: 47849S"()O

Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 20036

telephone 202-772-4900 facsimile 202-772-4979 www.exponcnt.com



### On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158 th 

### Plaza, Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies. Please find enclosed the following support documents:

• Transmittal document;

• EPA 8570-1;

• EPA 8570-27;

• Confidential Statement ofFormula (three copies);

• EPA 8570-34;

• Data Matrix;

• Draft Label (five copies); and

• Copy ofPRIA paperwork for 50% waiver/reduction and payment check.

As discussed with EPA during a meeting on August 19,2009, Sergeant's is submitting EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332- 3). The product has been formulated and labeled for application to dogs and puppies 4-20 pounds.

The enclosed application for registration is for a new end-use product (substantially-similar formulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review ofdata package within RD, PRIA review time frame 6 months, and

a fee of$4,578. Sergeant's qualifies for a PRIA fee waiver/reduction of50% (refer to OPP Decision Number D-408042).

### Ifyou have any questions, please contact me at 202-772-4932.

## ~~r;l'y' 

# /**_.!//L.~-**

Jan1es B. Messina

f , 

### Authorized Representative of . I



### . Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kimberly Nesci, EPA Bob Scharf, Sergeant's Kelly Hoskins, Sergeant's Larry Nouvel, Nouvel Rick Tinsworth, Exponent**~X'** 

# "

, . H, v**J~**Please read instructrons on reverse**bef~** Pfeting form Form Appr 

### ,. OMB No 2070 0060 Approval expires 05 31 98


### . . -
United States IZLRegistration OPP Identifier Number 

# EPA Environmental Protection Agency DAmendment Washington, DC 20460 

# o Other

Application for Pesticide

- Section 

### I

1. CompanylProduct**~'(§.e<:;** 2. EPA Product Manager 3. Proposed Classification**2517.~** R. Gebken 4. Company/Product (Name) PM# [ZjNone DRestricted EtofenproxiNylar Spot-On Flea and Tick for Dogs and Puppies 10 (30%)
5. Name and Address of Applicant (Include ZIP Code) 6. Expedited Review. In accordance with FIFRA Section 3(C)(3)(b)(I), my Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to:
2625 South 158th Plaza Omaha, NE 68130 EPA Reg. No. 69332-3

Product Name SPI #8208·55D 

# o Check ifthis is a new address

, Section II

D Amendment

- Explain below. D Final printed labels in response to Agency letter dated XX-XX-XX

D Resubmission in response to Agency letter dated

### XX-XX~XX D "Me Too" Application

D Notification

- Explain below. 

# C8J Other

- Explain below. Explanation: Use additional page(s) if necessary. (For section I and Section II.) Submission of a new end-use registration application.

Section III
1. Material This Product Will Be Packaged In: Child-Resistant Packaging Unit Packaging Water Soluble Packaging 2. Type of Container DYes' !2'J Yes DYes 

# o Metal DNo 

# o No !2'J No 

## k8J Plastic If "Yes" No. per If "Yes" No. per DGlass 'Certification must Unit Packaging wgt. Container Package wgt. Container DPaper be submitted 2.0mL 

## I 1-6 

## I Dother (Specify) Plastic Bag 3. Location of Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions !2'JLabel 

# o Container 2.0mL DOn Can DOn Labeling accompanying product 6. Manner in Which Label is Affixed to Product DUthograph DOther DPaper glued DStenciled Section 

### IV
1. Contact Point (Complete items directly below foridentification ofindividual to be contacted, ifnecessary, to process this app/icatiQn.)

, , 

### , Name Title**Tel~p1Clne** No. Cr,C';uJe Area Code) James Messina Authorized Representative (202) 772-4932
Certification b. U1:tfe'Application I certify that the statements I have made on this form and all attachments thereto are true, accurate and complete. i**~~geived** acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both**(~(amped)** under.aoutk able law. ' '



# - 2. Signte 

# V2

. 3. Title BY: 

### /I Authorized Representative 

### 7T 4.**Typed~e:** 5. Date: 

# CJ 

# ;/O/C1
James Messina

# EXponent

September 10,2009

Richard Gebken Product Manager 10 Document Processing Desk (REGFEE) Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
Subject: Submission ofa Section 3 Registration Application EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies

Dear Mr. Gebken: 478498·00

Exponent 1150 Connecticut Avenue, NW Suite 11 00 Washington, DC 20036

telephone 202-772-4900 facsimile 202-772-4979 www.exponent.com



### On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158th 

### Plaza, Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies. Please find enclosed the following support documents:

• Transmittal document;

• EPA 8570-1;

• EPA 8570-27;

• Confidential Statement ofFormula (three copies);

• EPA 8570-34;

• Data Matrix;

• Draft Label (five copies); and

• Copy ofPRIA paperwork for 50% waiver/reduction and payment check.

As discussed with EPA during a meeting on August 19,2009, Sergeant's is submitting EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332- 3). The product has been formulated and labeled for application to dogs and puppies 4-20 pounds.

The enclosed application for registration is for a new end-use product (substantially-similar formulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review of data package within RD, PRIA review time frame 6 months, and

a fee of$4,578. Sergeant's qualifies for a PRIA fee waiver/reduction of50% (refer to OPP Decision Number D-408042).

### If you have any questions, please contact me at 202-772-4932.**~~rely,** .i' ' /1 

## / A'/ l '. /j /" /.

_ fL_--,.- 

# -r; JmJes B. Messina A)1thorized Representative of '. Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kimberly Nesci, EPA Bob Scharf, Sergeant's Kelly Hoskins, Sergeant's Larry 

### Nouvel, Nouvel Rick Tinsworth, Exponent

### Data Transmittal Document:

Product:

Submitter:

Return to: Sergeant's EtofenproxlNylar Split-On Flea:md ':'irk for 

### Dogs and Puppies· 2517-NEW
Sergeant's Pet Care Products,**Ill~,** 

### (El'A**'~('mrany** 

### Number 2517) 2637 South 158th 

### Plaza Suite 100 Omaha, NE 68130-1703

James Messina Exponent 1150 Connecticut Ave., NW Suite 1100 Washington, DC 20036

Submittal Date: September 10, 2009

Volume Study Title MRID I 

### Efficacy of a water-based etofenprox spot-on against 47849801
_. 

### fleas and ticks on small dogs 2 Efficacy, at minimum dose rate, ofan etofenprox spot-on 47849802 

### against fleas and ticks on small dogs 3 Efficacy, at label dose volume and at minimum dose rate, " 

### ofan etofenprox spot-on against fleas and ticks on small 47849803 

### dogs 4 

### Evaluation ofSergeant's etofenprox squeeze-on against 47849804 

### fleas, ticks and mosquitoes on dogs 5 Efficacy of Sergeant's etofenprox squeeze-on against 47849805 

### Ixodes scapularis nymphs 6 Efficacy ofa 2 mL unit dose of Sergeant's etofenprox squeeze-on, applied at minimum dose rates, against fleas 47849808 

### and ticks on small dogs 7 Data analysis ofa dose titration to determine the relationship between dose rate ofetofenprox, when 47849807 

### applied as a spot-on to dogs, and the duration ofresidual efficacy against flea and tick reinfestation 8 Analyses ofefficacy and safety data to support labels claims for Sergeant's squeeze-on for small.dogs 47849808 

### containing etofenprox and pyriproxyfen 9 Companion animal safety evaluation on dogs of spot-on products containing multiple toxicants and insect growth 47849809 

### regulators 10 Residential exposure and risk assessment for a proposed 47849810 

### etofenprox spot-on product for dogsPlease read instructions on reverse befe. 

### ']**~** ompleting form Form Appr ..i OMS No 20700060 Approval expires**05~31** 98

- -
United States [gJ_Registration QPP Identifier Number 

# EPA Environmental Protection Agency D_Amendment Washington, DC 20460 D Other

Application for Pesticide

- Section I
1. Company/Product**~~e'G** 2. EPA Product Manager 3. Proposed Classification**2517-~** R. Gebken 4. Company/Product (Name) PM#

### ~None DRestricted EtofenproxiNylar Spot-On Flea and Tick for Dogs and Puppies 10 (30%)
5. Name and Address of Applicant (Inc/ude ZIP Code) 6. Expedited Review. In accordance with FIFRA Section 3(C)(3)(b)(I), my Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to:
2625 South 158 1h Plaza Omaha, NE 68130 EPA Reg. No. 69332-3

Product Name SPI #8208-55D

D Check ifthis is a new address Section II

D Amendment

### ~ Explain below. D Final printed labels in response to Agency letter dated XX-XX-XX

D Resubmission in response to Agency letter dated

### XX~XX-XX 

# D "Me Too" Application

D Notification

### ~ Explain below. 

## [ZJ Other

### ~ Explain below. Explanation: Use additional page(s) if necessary. (For section I and Section II.) Submission of a new**end~use** registration application.

Section III
1. Material This Product Will Se Packaged In:**Child~Resistant** Packaging Unit Packaging Water Soluble Packaging 2. Type of Container DYes' [:g] Yes DYes 

# o Metal DNo 

# o No [:g] No 

### cg] Plastic II "Yes" No. per II "Yes" No. per DGlass 'Certification must Unit Packaging wgt. Container Package wgt. Container DPaper be submitted 2.0mL 

## I 1-6 

## I Dother (Specify) Plastic Bag 3. Location of Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions [:g]Label D Container 2.0mL DOn Can DOn Labeling accompanying product 6. Manner in Which Label is Affixed to Product DLithograph DOther DPaper glued DStenciled Section IV 

### , n' 1. Contact Point (Complete items directly below for identification ofindividual to be contacted, ifnecessary, to process this applicatiQ{J.) :**~** 

### , , , Name Title**}T:e\tfn~ne** No. (trit1t..tle Area Code) James Messina Authorized Representative , 

### , (202) 71'2-4932



### , 

### ,**~** Certification ,," , t1') uate'l\pplication , I certify that the statements I have made on this torm and all attachments thereto are true, accurate and complete. 

### ,**)~~cpived** acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both } J ' ,**,(,~t'amped) under~**  able law. ' , 

## :" :'0- , 2. Signte 

# VZ 3. Title ' ' " ! ) ; 1
, BY: 

### /I Authorized Representative ) } }**~** 

### 7T , "
, , , 4.**Typed~e:** 5. Date: 

# <J;lo/tJ'f ,)' ,
James MessinaTracking
Create

FFS Letters

# \ NEW APPLICATIONS

DATE: SEP 102009



# FILE NUMBER: [)Sf7- 

# RGG



# FEP (OPPIN ENTRY)' jv 

# Cfjll/Or; 

# (Initial & 

# date) , 

# FILE, ROOM:

__**~**

# __ _ (Initial & 

# date)

SIG: 

# (Initial & 

# date)



# FILE ROOM:

__ ..,------__ _ (Initial & 

# date)



# / ASSIGN TO PM

-- 13 

# (NO DATA)



# _ JACKET TO 

# SHELF (DATA)

# To the Document Center (ITRMD) *Please transfer jacket /mini-jacket to Product Manager Team circled below:

Minor Use Section 

# PM- 5

Insecticide Branch 

# PM 

# -10 PM-13

Herbicide Branch 

# PM-23 PM-25

Fungicide Branch 

# PM

- 21 PM-22

Insect /Rodent Br

.. 

# PM-l PM-7

*Reminder to PM

- 

# If applicable pick-up data from Screening Room.

Processe by 

# RO's Completeness Check T am

# 21-Day Screen 

# Completed by 

# Contractor


# 21-Day Expires on 

# ;0 ---/-09



# Jacket # 

# c2 51 

# 7 - ;(&& MRID# L/79 Lf'7t:,



# Content Screen: Recommended to BFail



# 86-5 Review: lpassed-yFailed/NA



# Transfer This Jacket to:

# Memorandum

Date: 09 / 

# n / 09



# To:

____ P_M

__ ( 3

_____ , 

# Regulatory Manager

From: Information Services Branch, ITRJ\1D

Your receipt ofthis data submission is not an indication that lVIRIDs for the enclosed studies have

. been posted to OPPIN.

We expect that it 

# will 

# be approximately 5 days 

# from the above date before the study-level data is available in 

# OPPIN.

Ifyou have any questions about this process, please contact Teresa Downs (305-5363).

This is a:

# ~fullY accepted submission 

# o partially accepted submission 

# o rejected submission

### September 10, 2009

Richard Gebken Product Manager 10 Document Processing Desk (REGFEE) Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S·4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202·4501
Subject: Submission ofa Section 3 Registration Application EtofenproxlNylar Spot·On Flea and Tick for Dogs and Puppies

Dear Mr. Gebken: 478498·00

Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 20036

telephone 202-772-4900 facsimile 20.2-712-4979 w\\,cw.exponent.com



### On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 15Sth 

### Plaza, Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies. Please find enclosed the following support documents:

• Transmittal document;

• EPA 8570-1;

• EPA 8570·27;

• Confidential Statement ofFonnula (three copies);

• EPA 8570·34;

• Data Matrix;

• Draft Label (five copies); and

• Copy of PRIA paperwork for 50% waiver/reduction and payment check.

As discussed with EPA during a meeting on August 19,2009, Sergeant's is submitting EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332- 3). The product has been fonnulated and labeled for application to dogs and puppies 4-20 pounds.

The enclosed application for registration is for a new end-use product (substantially-similar fonnulation) with 

### supporting data. This registration application is considered an R31 0, new enduse product, requires review of data package within RD, PRIA review time frame 6 months, and

a fee of$4,578. Sergeant's qualifies for a PRIA fee waiverlreduction of 50% (refer to OPP Decision Number DA08042).

### Ifyou have any questions, please contact me at 202-772-4932.**~~rely,** ,f' )/] 

# '

.. ,-..**j~.i-** 

## pL._-.·

Janles B. Messina Aithorized Representative of
./



### Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kimberly Nesci, EPA Bob Scharf, Sergeant's Kelly Hoskins, Sergeant's Larry Nouvel, Nouvel Rick Tinsworth, Exponent

### Data Transmittal Document:



### Product:

Submitter:

Return to: Sergeant's EtofenproxlNylar SpLIt-On Flea and ':'irk fo' Dogs and Puppies 25 I7-NEW
Sergeant's Pet Care Products,**In~.** 

### (EpA**'~('mrany** 

### Number 2517) 2637 South 158th 

### Plaza Suite 100 Omaha, NE 68130-1703

James Messina Exponent 1150 Connecticut Ave., NW Suite 1100 

### Washington, DC 20036

Submittal Date: September 10, 2009

Volume Study Title MRID I 

### Efficacy ofa water-based etofenprox spot-on against 47849801 

### fleas and ticks on small dogs

. 

### 2 Efficacy, at minimum dose rate, ofan etofenprox spot-on 47849802 

### against fleas and ticks on small dogs 3 Efficacy, at label dose volume and at minimum dose rate,

r 

### ofan etofenprox spot-on against fleas and ticks on small 47849803 

### dogs



### - 4 

### Evaluation ofSergeant's etofenprox squeeze-on against 47849804 

### fleas, ticks and mosquitoes on dogs 5 Efficacy ofSergeant's etofenprox squeeze-on against 47849805 

### Ixodes scapularis nymphs 6 Efficacy ofa 2 mL unit dose of Sergeant's etofenprox squeeze-on, applied at minimum dose rates, against fleas 47849808 

### and ticks on small dogs 7 Data analysis ofa dose titration to determine the relationship between dose rate ofetofenprox, when 47849807 

### applied as a spot-on to dogs, and the duration ofresidual efficacy against flea and tick reinfestation 8 Analyses ofefficacy and safety data to support labels claims for Sergeant's squeeze-on for small dogs 47849808 

### containing etofenprox and pyriproxyfen 9 Companion animal safety evaluation on dogs of spot-on products containing multiple toxicants and insect growth 47849809 

### regulators 10 Residential exposure and risk assessment for a proposed 47849810 

### etofenprox spot-on product for dogsUr.:lfC S:4('1**E"~'liOr,n:-"** ,'P'C'it:(I\J..- t..:;'ln:! Olilet 0) Pn!JcIG' ":OQ:JJlll ir-;!OH"J; Ilor F.., lour:-. i .1IC S.·

...... ,;: II c':"YI1,on lroI OlfTH II0ro**S';"~IC.tl ei~('"".~,**  

# & 

# EPA**AD~1J:N1S1RATIVE ~TO(S),:**  •

).5'11- ReG



# Pl\.{: --,-!3

____ -----;:---

____**~**

# __


# C TIT}nc AT}

# TO·· •**r&~**

# yu i

... J..J...../ 

## 1" ,. _________**~**

## _____ _



# The jacket for this 

# action can be requested through the JACKETS 

# s·ystem.

## PRIA 2 - 21 Day Content Screen Review Worksheet (EPNOPP Use Only) 3/23/09 21 Day Screen Start Date: 

# 9 - 10

- 

## a 9 ./ Experts In-Processing Signature: ME JI;-zaJvAl6/U-v Date 

### 9- -/'>-0'7 Fee Paid: Yes_ V Division management contacted on issues No Yes Date

_____ _

EPA Reg. Number: 

## ?. 

## SI,

- 12. 

## GG EPA Receipt Date: 

# 9-/0-09

Items for Review Yes No



### 1 Application Form (EPA Form 8570-1)(link to forn1) signed & complete 

# X including package type

Confidential Statement of Formula all boxes completed, form signed, and 

# X
dated (EPA Form 8570-4) (Link to form) 2 a) All inerts (link to http://www.epa.gov/opprd001/inerts/), yes no including fragrances, approved for the proposed uses (see 

# X Footnote A)

••••• Certificatiou with Respect to Citation of Data (EPA Form 8570-34) (Link to 

# X 3 form) completed and signed (N/A if 100% repack)

Certificate and data matrix consistent 

# >c

Ifapplicant is relying on data that are compensable, is the offer yes no to pay statement included. (see Footnote B)

If "". nhk is there a letter ofAuthorization for exclusive use only. Formulator's Exemption Statement (EPA Form 8570-27) 

### (Link to fonn) 4 completed and signed (NI A ifsource is unregistered or applicant owns the 

# X
-'- -, i1)

Data Matrix (EPA Form 8570-35) (Link to fonn) both internal and external 

# X copies (PR 98-5) (Link to PR 98-5) completed and signed (N/A if 100% 

### N/A*

"'c)
5 yes no· 

# aJ.i•..:,,' a) Selective Method (Fee category t;Jl.jJ'" lS use) 

# X

# llif~~~~~ b) Cite-All (Fee category experts use) 

# r,;c c) Applicant owns all data (Fee category experts use) '7



### . ,-,\,' 

## .•. ",;.'

5 Copies of Label (link to htt[!:llwww.eI!a.gov/oImfeadlllabelinv'lrmD 

# X 6 (Electronic labels on CD are encouraged and guidance is available)( link to http://www.epa.gov/peslicides/regulatinglregislering/submissions/index.hlm#labels )

1 ,

### 7 Is the data package consistent with PR Notice 86-5 (link to PRN 86-5) 

# X

Notice ofFiling (link to 8 httn:llwww.ena.gov/nesticides/regulatingLtolerance netitions.htm) included 

# k with petitions (link to http://www.epa.gov/pesticides/regulating/tolerances.htm)
9 If

### applicable for conventional applications, reduced risk rationale (link to 

# X http://,,,,",w.epa.gov/opprdOOl/workplanireducedrisk.html)
Required Data (link to httn:II",,",w.ena.gov/nesticides/regulatingLdata reguirements.htm) and/or data waivers. See Footnote C.

a) 

### List study (or studies) not included with application



### 10

!

2

### Comments;



## * NI 

### A - Not Applicable

Footnotes 0../V1 0

## ~"'--**~d** GO

## ~ 

# -\-e,- 

# +R:- s 

### PIU0

- '2G-S

## ~v~·

A. During the 21 day initial content review, all eSFs will be reviewed to determine whether all inerts listed, including fragrances, are approved for the proposed uses. Ifan unapproved inert is identified, the applicant must either I) resolve the inert issue by, for example, removing the inert, substituting it with an approved inert, submitting documentation that EPA approved the inert for the proposed pesticidal uses, correcting mistakes on the eSF, etc. or 2) provide the data to support 

### OPP approval ofthe inert or 3) withdraw the application. Removing or substituting an inert ingredient will require a new eSF and may require submission ofdata. All information, forms, data and documentation resolving the inert issue must have been received by the Agency or the application withdrawn within the 21 day period, otherwise, the Agency will reject the application as described below.

To successfully complete 

### this aspect ofthe 21 day initial content screen, applicants are strongly encouraged to verify that all inert ingredients have been approved for the application's uses even if a product is currently registered by consulting the inert Web
3i**~** 

### site [link to http://www.epa.gov/opprdOOliinertsllists.html] and ifthe inert is not approved, to obtain the necessary inert approval prior to submitting an application to register a pesticide product containing that inert ingredient. Some inert ingredients are no longer approved for food uses or certain types ofuses. The name and/or CAS number on a CSFmust match the name and CAS number on this web site. Simple typographical errors in the name or CAS number have resulted in processing delays.

Ifan inert is not listed on the inert ingredient web site and the applicant believes that the inert has been approved, the applicant should contact the Inert Ingredient Assessment Branch (IIAB) at inertsbranch@epa.gov and resolve the issue. Copies ofthe correspondence with IIAB resolving the issue should accompany the application. All
new inerts except PIP inerts are reviewed by nAB. The IIAB should also be contacted for anyquestions on what supporting data needs to be submitted for and the Agency's inert review process. Questions on PIP inerts should be directed to the Chiefof Microbial Pesticides Branch [Link to http://www.epa.gov/oppbppdllbiopesticides!contactsbppd.htm].

When a brand, trade, or proprietary name ofan inert ingredient is listed on a CSF, additional information such as an alternate name ofthe inert, CAS number or other information [link to http://www.epa.gov/opprd001/inerts/tips.pdt] must also be included to enable the Agency to determine ifit has been approved. Each component ofan inert mixture (including a fragrance) must be identified. In 

### some cases, the supplier ofthe mixture or fragrance may need to provide this information to the Agency. Prior to the Agency's receipt ofan application, applicants must arrange with a proprietary mixture or fragrance supplier to provide the component information to the Agency or promptly upon EPA's request. Ifthe inert ingredients in a proprietary blend (including fragrances) carmot or are not identified or provided within the 21-day content review period, the Agency will reject the application.
During the 21 day content review, applicants should submit information to the individual identified by the Agency when the applicant is informed ofan unapproved inert.
Unapproved Inerts Identified on CSFs

All applications except conventional new products and PIPs

Once an unapproved inert is identified on a CSF, the Agency will contact the applicant with the following options:

I. Correct the application by, for instance, correcting the inert's identity or CAS number, providing documentation that the inert has been approved, or removing the unapproved inert from the CSF or replacing it with one that is approved for the application's uses; or

2. Submit the information and data needed for the Agency to approve the unapproved inert Ifthis option is selected and implemented, the Agency may request an extension in the PRIA decision review timeframe to accommodate the inert review/approval process;



### 4

### 3. Withdraw the application (the Agency retains 25% ofthe full fee for the fee category estimated); or

Ifnone ofthese options is selected and implemented by the applicant within the 21 day content review period, the Agency will reject the application and retain 25% ofthe full fee ofthe category identified.

Conventional New Product Applications

When the Registration Division identifies an unapproved inert on a CSF with an application for a new product that the applicant has not identified as requiring an inert approval (R311 , R312 or R313), it will contact the applicant with the following options:

1. Correct the application by, for instance, correcting the inert's identity or CAS number, providing documentation that the inert has been approved, or removing the unapproved inert from the CSF or replacing it with one that is approved for the application's uses; or

2. Submit the information and data needed for the Agency to approve the unapproved inert, including any required petition to establish or amend a tolerance or exemption from a tolerance. (This option may change the PRIA category for the application, which could require a longer decision review time and a larger fee. If additional fees are due, they must be received by the Agency within the 21 day content review period.)

3. Withdraw the application (the Agency retains 25% ofthe full fee for the fee category estimated); or

Ifnone ofthe above options is selected and implemented during the 21-day content-review period, the Agency will reject the application and retain 25% of the appropriate fee for the new product-inert approval category.

PIP Applications

When the Biopesticide and Pollution Prevention Division identifies an unapproved inert on a PIP CSF and a request to approve the inert does not accompany the application, it will contact the applicant with the following options:

1. Correct the application by, for instance, correcting the spelling or name ofthe inert to that in 40 CFR 174, or providing documentation that the inert has been approved; or

2. Submit the information and data needed for the Agency to approve the unapproved inert. Ifan inert ingredient tolerance exemption petition is required, the petition must be received by the Agency and the B903 fee paid within the 21 day period. Ifthis option is selected and implemented, the Agency will discuss harmonizing the timeframe for both actions. 5

### 3. Withdraw the application (the Agency retains 25% ofthe full fee for the fee category estimated); or

Ifnone ofthe above options is selected and implemented during the 21 day content review period, the Agency will reject the application and retain 25% of the fee.

B. A policy on documentation ofoffers to pay is still being developed, however, for a me-too or fast track (similar/identical) new product, R300 or A530, an application without the necessary authorizations ofoffers to pay will be placed into either R30! or A53!. The Agency recommends that authorizations ofoffers to paybe submitted with other PRIA applications to avoid delays in the Agency's decision.

C. 

### Biopesticide applicants are advised to contact the Agency and discuss study waivers prior to submitting their application to the Agency. Documentation ofsuch discussions should be submitted with the study waiver.

6Ms. Balan, RE: Submissiou to EPA .James Messina to: Aswathy Balan Cc; Sree Nair

As discussed today, please fmd attached the requested pages.

Ifyou have any questions, please contact me at 202-772A932.

Best Regards, Jim
-----Original Message----- From: Balan.Aswathy@epamail.epa.gov [mailto:Balan.Aswathy@epamail.epa.gov

### 1 Sent: Thursday, September 17, 2009 II:II AM To: James Messina Cc: Nair.Sree@epamail.epa.gov Subject: Submission to EPA

Hi Mr. James,

This is a follow-up email regarding your Application for Registration of the products Cyphenothrin + Methoprene Squeeze-on for Dogs(30%) (EPA Reg No: 2517-REI), and EtofenproxlNylar Spot-on Flea and Tick for Dogs and Puppies(30%) (EPA Reg No:2517-RGG). We have found the following deficiencies regarding your submissions.
Cyphenothrin + Methoprene Squeeze-on for Dogs(30%) (EPA Reg No: 2517-REI)

1. The Application form (EPA Form 8570-1) is missing.
EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies(30%) (EPA RegNo:2517-RGG)

l.ln Study #9: Companion animal safety evaluation on dogs ofspot-on products containing multiple toxicants and insect growth regulators: Your No claim ofconfidentiality statement is contradicted by the marking(s) on pages 112-129 ofthe study. So please send me the confidentiality statement (page 2) with the following statement added to it:

This statement ofconfidentiality supersedes all confidentiality claims that you may fmd elsewhere in this report.

You can send me the form and corrected page either by fax to 703-305-5060, Attn: Aswathy Balan or email to balan.aswathy@epa.gov.

Thanks,
Aswathy Balan Data Analyst (EPA Contractor) 2777 S. Crystal Drive, S6943 09117/200901:02 PMArlington, VA 22202 Ph: 703-347-8787 Fax: 703-305-5060 Email: balan.aswathy@epa.goY

8750-1 Cyphenothrin+Methoprene.pdf sergeant no datac::onfstate:ment.pdf

### S, )t for Rej,ection Phone calls

Contact Name: 

## ::Jo.1'V\u, 

## 8, Mf>:<;,o,., "'- Phone #: ;'Oc:'{

- '11 

### Q - lj9 

### 2> :;J.. 

### Email: 

# j ""<' 55;V\.R@ 

# e'lLp" Vle.,1, U:l Iv\.


### First 

### CallIInitWs: AB Date: 09 

## It'1 

# r D9 

### Time: I r : 05 AN 

### Second CallJInitials: Date: Time:

This is,

__ cA_g_(,{)--=..;<A-!;.;..'-=l-C-f1_:R_0-_1_<A.._Vo-

____ --', 

### EPA contractor.

I'm calling regarding your submission in 

### support of

fLu

## lJ<..,\.t'f;y,,-~**~**

# b l""O!L"h -;> o>S!/ - R EJ 

## Q",-tf

We have found the following deficiencies regarding: PR Notice 86.5: @rNo

# 0o~:m~:~~y~~~:**~ .s\'-'-~** **~** 9: 

# tv\- 

# \')1" \\:{-**\~~, ~''''''Srl~~~1** **'\Ab.'15k:'~ r~"'\:** **cs~,to** 

## t",,>[-iALt**,t~** lVe 

### ,-l<U'N) 

# 6b Volume/Study Title: (j

## ('~

# G cl..**v~**U

### 'oj;,

# -L1 .0

## to- 

# t.**(l~** ...

### t

## t;~ -\-k, <;'

# W(j

.

Volume/Study Title:

Additional volumes continued on back ofpage: Yes or No Application Package@or No ' 

# CD \tI<- .Q5T1- R E: 

### 1 

## =7 

# Arr\r'La\. d-;"" 

# 16'<Y'<> 

# IS 'vv..

# ~ ~ 5,

# ~D(} 

# ,

These deficiencies have been approved by EPA. 

# A The corrections can be faxed to 703-305-5060/ 

### Attn: 

# "\N0... 

## tt-, '--\ \ 

### Second CallIEmail: Ifwe do not receive the'corrections by , we will 

### process your, submission, accordingly. Please direct all future calls and correspondence to the appropriate EPA Risk Manager.UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460



### September 14, 2009

OPP Decision Number: D-420097 EPA File Symbol or Registration Number: 2517-RGG OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES



### Product Name: ETOFENPROXINYLAR SPOT-ON FLEA AND TICK FOR DOGS & 

### PUPPIES(30%) EPA Receipt Date: 10-Sep-2009 EPA Compauy Number: 2517 Compauy Name: SERGEANT'S PET CARE PRODUCTS, INC.EPA File Symbol or Registration Number:

KELLY R. HOSKINS SERGEANT'S PET CARE PRODUCTS, INC. 2625 SOUTH 158TH PLAZA OMAHA, NE 68l30-1703

SUBJECT: Receipt ofApplication aud 50% Small Business Waiver Request
De!jf Registraut:

The Office ofPesticide Programs has received your application, 50% small business waiver re'lllest, aud cerification ofpayment. Ifyou submitted data with this application, the results ofthe pRN-86-5 screen will be communicated separately. During the administrative screen, the Office ofPesticide Programs has determined that this Action is subject to a Pesticide Registration Service Fee as defined in the Pesticide Registration Improvement Act.

The Action has been identified as Action Code: R31 0

NEW PRODUCT;NON-FAST TRACK (INCLUDES REVIEWS OF PRODUCT CHEMISTRY;ACUTE TOXICITY;PUBLIC HEALTH PEST EFFICACY);

Your request for waiver has been forwarded for review. You will be notified in writing when a determination is made regarding your request. Ifyour waiver request is approved, the decision review time period will start on the date ofapproval. Ifyour waiver request is denied, you will receive au invoice for the outstauding balauce.

Ifyou have any questions, please contact the Pesticide Registration Service Fee Ombudsmau at (703) 305-6249. ,:/:

# IFee for Servicel 

# -'**{857902+~**

This package includes the following for Division

## ~ 

# New Registration oAD

o Amendment oBPPD**~RD**

# ~Fee Waiver?**~** 

# Studies? 

# [ill -J 

# Risk Mgr. Dvolpay % 

# Reduction: 

# 50!

v 

# Receipt No. 

# s-I 857902 

# I
EPA File Symbol/Reg. No. 

# I 2517-RGG 

# I Pin-Punch Date: 

# I 9/10/2009 

# I



# o This item is NOT subject to FFS action. Parent/Child Decisions: Requested: 

# I IZ 3/ 

# D
Granted: 

# I K '31 0 

# I

Amount Due: 

# $

# Y~-lt{J'9,JfV

Uncleared Inert in Product**Reviewer:_----'-~_==_____==_** 

## ____ _ Date: 

# O(-! 

# If-

# Dr

Remarks:**Ap_pli~'Stbn"D,~e,: lront~nCl**  Date: FFS'DueOate:**OPPT~rgatDate:** "astIrack:. 

## r 

# F O-Sep-2009**~** 1-Sep-2009 

### 1 Fee For Servic'e:**'r."'f{~;l** 

### r No
>BaI,sble: 

### it**Y~i'** C No

Me To'(f ""
, , Product Name: jSPI#8208"5SD

OPPRec'vd Date:**~isK Man~gerSe'nd**  Date:**N¢~QUated',Clue'** Date:



## r T

,**Receipt''DE;~criPtion: ~~--------~--~~--~~--------­**  ubmission of a new end-use registration application

FormA 

## r Print Letter

Enter More Information

.. RecOlplConl"nt**~OdY·····················** fSF Tracking

View/Edit

# FEE FOR 

# SERVICE

### September 10, 2009

U.S. Bank FIFRA Service Fees Government Lockbox 979074 1005 Convention Plaza SL-MO-C2-GL St. Louis, MO 63197 (314) 418-4990
Subject: Submission ofEPA Pesticide Registration Improvement Act Fees

U.S. EPA FIFRA Service Fees: Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 2C036
telephone 202-772-4900 facsimile 202-772-4979 www.exponent.c0l1l



### On behalf of our client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158th 

### Plaza, Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting Pesticide Registration Improvement Act Fees for the following new registration applications:

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin+Methoprene Squeeze-On for Dogs (20%), check #426591;

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin+Methoprene Squeeze-On for Dogs (30%), check #426592;

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin+Pyriproxyfen Squeeze-On for Dogs (20%), check #426593;

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin+Pyriproxyfen Squeeze-On for Dogs (30%), check #426594;

• R31O, $4,578 (50% fee waiver $2,289), Cyphenothrin Squeeze-On for Dogs (20%), check #426595;

• R310, $4,578 (50% fee waiver $2,289), Cyphenothrin Squeeze-On for Dogs (30%), check #426596; and

• R310, $4,578 (50% fee waiver $2,289), Etofenprox/Nylar Spot-On Flea and Tick for Dogs and Puppies, check #426597.

Each ofthe registration applications are for a new end-use product (substantially-similar formulation) with supporting data. They are all considered an R31 0, new end-use product, requires review ofdata package within RD, PRIA review time frame 6 months, and a fee of $4,578. Sergeant's qualifies for a PRIA fee waiverlreduction of 50% (refer to OPP Decision Number D-408042).

The total amount ofthe combined PRIA fee payments is $11,445.

### If you have any questions, please contact me at 202-772-4932.**Sin,ce~el**

### y,

. /' (



### James B. Messina ,.Authorized Representative of Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kimberly Nesci, EPA Richard Gebken, EPA Bob Scharf, Sergeant's Kelly Hoskins, Sergeant's Larry Nouvel, Nouvel Rick Tinsworth, ExponentPetCareProducts,Inc.Omaha,NebraskaPayfP6Co11'1"'111t/?.;Il-TexasCapitalBankHillCountryTwoThousandTwoHundredEightyNineDollarsAnd00/100EPA1149426597VOIDAFTER180DAYSTWOSIGNATURESREQUIREDFORAMOUNTSOVER$25,00000totheorderofWASHINGTONFINANCECTRFIFRASERVICEFEESPOBOX979074STLOUIS,MO63197-90001I'42bS'l711'557541

### Data Transmittal Document:

Product:

Submitter:

Return to: Sergeant's Etofenprox/Nylar Sput-On Flea ond ':'ick fo' Dogs and Puppies 25 I7-NEW
Sergeant's Pet Care Products,**In~.** (El'A**'~Qmpany** Number 2517) 2637 South 158th Plaza Suite 100 Omaha, NE 68130-1703

James Messina Exponent 1150 Connecticut Ave., NW Suite 1100 Washington, DC 20036

Submittal Date: September 10, 2009



### Volume Study Title MRID I Efficacy of a water-based etofenprox spot-on against fleas and ticks on small dogs 2 Efficacy, at minimum dose rate, of an etofenprox spot-on against fleas and ticks on small dogs 3 Efficacy, at label dose volume and at minimum dose rate, of an etofenprox spot-on against fleas and ticks on small dogs 4 Evaluation of Sergeant's etofenprox squeeze-on against fleas, ticks and mosquitoes on dogs 5 Efficacy of Sergeant's etofenprox squeeze-on against Ixodes scapularis nymphs 

### 6 Efficacy ofa 2 mL unit dose of Sergeant's etofenprox squeeze-on, applied at minimum dose rates, against fleas and ticks on small dogs 7 Data analysis of a dose titration to determine the relationship between dose rate ofetofenprox, when applied as a spot-on to dogs, and the duration ofresidual efficacy against flea and tick reinfestation 8 Analyses ofefficacy and safety data to support labels claims for Sergeant's squeeze-on for small dogs containing etofenprox and pyriproxyfen 9 Companion animal safety evaluation on dogs of spot-on productscontaining multiple toxicants and insect growth regulators 10 Residential exposure and risk assessment for a proposed etofenprox spot-on product for dogsPlease read instructions on reverse bef6 ) or ;eting form

",- Form Appr " .I. -.../!iJ1B No 20700060 Approval expires 05 31 98



### - - -
United States ISLRegistration OPP Identifier Number 

# EPA Environmental Protection Agency D.Amendment Washington, DC 20460 

# o Other
Application for Pesticide

- Section I

1. Company/Product**~~erG** 2. EPA Product Manager 3. Proposed Classification**2517-~** R. Gebken 4. Company/Product (Name) PM#

### ~None DRestricted EtofenproxiNylar Spot-On Flea and Tick for Dogs and Puppies 10 (30%)
5. Name and Address of Applicant (Include ZIP Code) 6. Expedited Review. In accordance with FIFRA Section 3(C)(3)(b)(I), my Sergeant's Pet Care Products, Inc. product is similar or identical in composition and labeling to:
2625 South 158th Plaza Omaha, NE 68130 EPA Reg. No. 69332-3

Product Name SPI #8208-55D

D Check ifthis is a new address Section II

D Amendment

- Explain below. D Final printed labels in response to Agency letter dated XX-XX-XX 

# D Resubmission in response to Agency letter dated XX-XX-XX D "Me Too" Application

D Notification

- Explain below.

### ~ Other

- Explain below. Explanation: Use additional page(s) if necessary. (For section I and Section II.) Submission of a new end-use registration application.

Section III
1. Material This Product Will Be Packaoed In: Child-Resistant Packaging Unit Packaging Water Soluble Packaging 2. Type of Container DYes' [8J Yes DYes DMetal DNo 

# o No [8J No 

### [8J Plastic If "Yes" No. per If "Yes" No. per DGlaSS *Certification must Unit Packaging wgt. Container Package wgt. Container DPaper be submitted 2.0mL 

## I 1-6 

## I DOther (Specify) Plastic Bag 3. Location of Net Contents Information 4. Size(s) Retail Container 5. Location of Label Directions [8JLabel D Container 2.0mL DOn Can DOn Labeling accompanying product
6. Manner in Which Label is Affixed to Product DUthograph DOther DPaper glued DStenciled Section IV
1. Contact Point (Complete items directly below for identification ofindividual to be contacted, ifnecessary, to process this app/icatiQn.) \ \



### , Name Title**T~!ep'')ne** No. (':r,c';uJe Area Code) James Messina Authorized Representative (202) 712-4932

Certification b. U1:!(e' Application I certify that the statements I have made on this form and all attachments thereto are true, accurate and complete. i**~'2eived** acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both (stamped)**under~** able law.



# -- 2. Signtre 

# v:z '. 3. Title
BY: 

### II Authorized Representative 

### 7T
4.**Typed~e:** 5. Date: 

# '1;/0/01 James MessinaForm approved. OMB No. 2070·0060, 2070-006"

...070-0107, 2070·0122, 2070-0164. 

# & 

# EPA

United States Environmental Protection Agency Washington, DC 20460 Formulator's Exemption Statement (40 CFR 152.85)

Applicant's Name and Address EPA File Symbol/Registration Number Sergeant's Pet Care Products, Inc. 2517-NEW
2625 South 158th Plaza Product Name Omaha, NE 68130 EtofenproxINylar Spot-On Flea and Tick For Dogb

Date of**COqi;I:~m;nt** of Fonnula 

# (EPA Form 8570-4)

As an authorized representative of the applicant for registration of the product identified above, I certify that:
(1) This product contains the following active ingredient(s): Etofenprox and Pyriproxyfen

(2) Of these, each active ingredient fisted in paragraph (4) is present solely as the result of the use of that active ingredient in the manufacturing, formulation or repackaging another product which contains that active ingredient which is registered under FIFRA Section 3, is purchased by
us from another person and meets the requirements of 40 CFR section 158.50(e)(2) or (3).
(3) Indicate by checking (A) or (B) below which paragraph applies:

71 (A) An accurate Confidential Statement of Formula (EPA FORM 8570·4) for the above identified product is attached to this statement. That formula statement indicates, by company name, registration number, and product name, the source of the active ingredient(s) listed in paragraph (1). OR



# ., (8) The Confidential Statement of Formula (CSF)(EPA Form 8570·4) referenced above and on file with the EPA is complete, current, an accurate and contains the information required on the current CSF.

(4) The following active ingredients in this product qualify for the formulator's exemption.

Source

Active Ingredient Product Name Registration Number Etofenprox



### , Pyriproxyfen P' ,



### , H 

### ,

)' " " ; t :>



# . •



# . , ,

, , , ,}, 1l) i 

### ,

} ) '} ,**Sign~re** 

# t21. Name and Title 

# Da:J.ioio7 , 

# .. James Messina, Authorized Rep.
/ 

# ----- D ) ff , } EPA FOr570-27 (Rev. 06-2004) Copy 1 -.tF:PI'; , Copy 2 - Applicant copy ) ,;

j F'Form Approved OMB Nos. 2070-0060; 2070-0057; 2070-0107; 2070-0 t22· 2070-0164

.............. UNITED STATES ENVIRONMENTAL PROTECTION AGENCY**(~)** "I._v"#" 1200 Pennsylvania Avenue, N.W. WASHINGTON, D.C. 20460

Paperwork Reduction Act Notice; The public reporting burden for this collection of information is estimated to average 1.25 hours per response for registration and 0.25 hours per response for reregistration and special review activities, including time for reading the instructions and completing the necessary fonns. Send comments regarding burden estimate or any other aspect ofthis collection of infonnation, including suggestions for reducing the burden to: Director, Collection Strategies Division (2822T), U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, N.W., Washington, DC 20460. Do not send the completed fonn to this address.

Certification with Respect to Citation of Data
Applicant's/Registrant's Name, Address, and Telephone Number EPA Registration Number/File Symbol Sergeant's Pel Care Products, Inc., 2625 South 158th Plaza, Omaha, NE 68130 2517·NEW
Aclive InQredient(s) and/or representative test compound{s) Date Etofenprox and Pyriproxyfen 9/10/09
General Use Pattern(s) (list all those claimed for this product using 40 CFR Part 158) Product Name Indoor non-food EtofenproxlNylar Spot-On Flea and Tick for Dogs D
NOTE: Ifyour product is a 100% repackaging of another purchased EPA-registered product labeled for all the same uses on your label, you do not need to submit this form. You must submit the Formulator's Exemption Statement (EPA Form 8570-27). 

# 0 I am responding to a Data-Call-In Notice, and have induded with this form a list of companies sent offers of compensation (the Data Matrix form should be used for this purpose).

SECTION I: METHOD OF DATA SUPPORT (Check one method only) 

# 0 I am using the cite-all method of support, and have included with this form 

## [2] I am using the selective method of support (or cite-all option
a list of compan·les sent offers of compensation (the Data Matrix form under the selective method), and have included with this form a should be used for this purpose). completed list of data requirements (the Data Matrix form must be used).

SECTION 11: GENERAL OFFER TO PAY
[Required if using the cite-all method or when using the cite-all option under the selective method to satisfy one or more data requirements] 

# 0 I hereby offer and agree to pay compensation, to other persons, with regard to the approval of this application, to the extent required by FIFRA.

SECTION Ill: CERTIFICATION

I certify that this application for registration, this form for reregistration, orthis Data-Call-In response is supported by all data submitted or cited in the application for registration, the form for reregistration, or the Data-Call-In response. In addition, ifthe cite-all option or cite-all option under the selective method is indicated in Section I, this application is supported by all data in the Agency's files that (1) concern the properties or effects ofthis product or an identical or substantially similar product, or one or more ofthe ingredients in this product; and (2) is a type of data that would be required to be submitted under the data requirements in effect on the date of approval of this application if the application sought the initial registration of a product of identical or similar composition and
uses.

I certify that for each exdusive use study cited in support ofthis registration or reregistration, that I am the original data submitter or that I have obtained the written permission of the original data submitter to cite that study.

I certify that for each study cited in support of this registration or reregistration that is not an exclusive use study, either: (a) I am the original data submitter; (b) I have obtained the permission of the original data submitter to use the study in support ofthis application; (c) all periods of eligibility for compensation have expired for the study; (d) the study is in the public literature; or (e) I have notified in writing the company that submitted the study and have offered (I) to pay compensation to the extent required by sections 3(c)(1)(F) and/or 3(c)(2)(B) of FIFRA; and (il) to commence negotiations to determine the amount and terms of compensation, if any, to be paid for the use ofthe study.

I certify that in all instances where an offer of compensation is required, copies of all offers to pay compensation and evidence of Iheir delivery in accordance with sections 3(c)(1)(F) and/or 3(c)(2)(B) of FIFRA are available and will be submitted to the Agency upon request. Should I fail to produce such evidence to the Agency UpOn request, I understand that the Agency may initiate action to deny, cancel or suspend the registration of my product in conformity with FIFRA

I certify that the statements I have made on this form and all attachments to it are true, accurate, and complete. I acknowledge that any knowingly false or misleading statement may be punishable by fine or imprisonment or both under applicable law.**~** Signature 

# ( 

# rL
, Date Typed or Printed Name and Title 9/10/09 James Messina, Authorized Representative

EPA Form 8570-34 (1213) Electronic and Paper versions available. Submit only Paper version.

# EXponenr

September 10, 2009

Richard Gebken Product Manager 10 Document Processing Desk (REGFEE) Office ofPesticide Programs (7504P) U.S. Environmental Protection Agency Room S-4900, One Potomac Yard 2777 South Crystal Drive Arlington, VA 22202-4501
SUbject: Submission of a Section 3 Registration Application EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies

Dear Mr. Gebken: Exponent 1150 Connecticut Avenue, NW Suite 1100 Washington, DC 20036

telephone**202~772-4900** facsimile 202-772-4979 www.exponent.com



### On behalfofour client, Sergeant's Pet Care Products, Inc. (Sergeant's, 2637 South 158'h Plaza, Suite 100, Omaha, NE 68130-1703, EPA Company Number 2517), Exponent is submitting a Section 3 registration application for the product EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies. Please find enclosed the following support documents:

• Transmittal document;

• EPA 8570-1;

• EPA 8570-27;

• Confidential Statement ofFormula (three copies);

• EPA 8570-34;

• Data Matrix;

• Draft Label (five copies); and

• Copy ofPRIA paperwork for 50% waiver/reduction and payment check.

As discussed with EPA during a meeting on August 19, 2009, Sergeant's is submitting EtofenproxlNylar Spot-On Flea and Tick for Dogs and Puppies as a substantially-similar product to the currently registered pesticide product SPI #8208-55D (EPA Registration Number 69332- 3). The product has been formulated and labeled for application to dogs and puppies 4-20 pounds.

The enclosed application for registration is for a new end-use product (substantially-similar formulation) with supporting data. This registration application is considered an R31 0, new enduse product, requires review ofdata package within RD, PRIA review time frame 6 months, and

a fee of$4,578. Sergeant's qualifies for a PRIA fee waiver/reduction of50% (refer to OPP Decision Number D-408042).

### If you have any questions, please contact me at 202-772-4932.

### /~relY, 

# 1".--I41l"---",,

JMs B. Messina 4jthorized Representative of Sergeant's Pet Care Products, Inc.

Enclosures

cc: Kimberly Nesci, EPA Bob Scharf, Sergeant's Kelly Hoskins, Sergeant's Larry Nouvel, Nouvel Rick Tinsworth, ExponentFormApprovedOMBNo.2070-0060UNITEDSTATESENVIRONMENTALPROTECTIONAGENCY""-401MStreet,S.W.WASHINGTON,D.C.20460PaperworkReductionActNotice:Thepublicreportingburdenforthiscollectionofinformationisestimatedtoaverage0.25hoursperresponseforregistrationactivitiesand0.25hoursperresponseforreregistrationandspecialreviewactivities,includingtimeforreadingtheinstructionandcompletingthenecessaryforms.Sendcommentsregardingtheburdenestimateoranyotheraspectofthiscollectionofinformation,includingsuggestionsforreducingtheburdentoDirector:OPPEInformationManagementDivision(2137)U.S.EnvironmentalProtectionAgency,401MStreet,S.W.,Washington,DC20460.Donotsendtheformtothisaddress.DATAMATRlXDate:September10,2009EPARegNo.lFileSymbol2517-NEWPage1of2Applicant's/Registrant'sName&AddressProduct:Etofenprox/NylarFleaandSergeant'sPetCareProducts,Inc.2637South158thPlaza,Suite100,Omaha,NE68130-1703TickforDogsandPuppiesIngredients:EtofenproxandPyriproxyfenGuidelineReferenceNumberGuidelineStudyNameMRIDNumberSubmitterStatusNote830.1550,1600,1620,1650,ProductPropertiesData46161301Sergeant'sPetCareProducts,Inc.OWN1670,1750,1800830.6302,830.6303,830.6304,Productchemistry46161302Sergeant'sPetCareProducts,Inc.OWN830.7300, 830.7000, 830.6315,830.7100,830.6320,830.6317830.6317,830.6320Storagestabilityandcorrosioncharacteristics46700801870.1100Acuteoraltoxicity46161303Sergeant'sPetCareProducts,Inc.OWN870.1200Acutedermaltoxicity46161304Sergeant'sPetCareProducts,Inc.OWN870.1400Primaryeyeirritation46161305Sergeant'sPetCareProducts,Inc.OWN870.1500Primarydermalirritation46161306PetCareProducts,Inc.OWN870.1600Dermalsensitization46161307Sergeant'sPetCareProducts,Inc.OWN870.7200CompanionAnimalSafetyEvaluationonDogsNewsubmissionSergeant'sPetCareProducts,Inc.OWN810.3300Efficacyofawater-basedetofenproxagainstNewsubmissionSergeant'sPetCareProducts,Inc.OWNfleasandticksonsmalldogsResidentialexposureandriskassessmentforaNewsubmissionSergeant'sPetCareProducts,Inc.OWN-----proposedetofenproxspot-onproductfordogsSignature:"11_NameandTitleJamesMessina,AuthorizedRepresentative_n._n__n",_,-.,•..'<.••-,,-••••_ T••___,..._1"""__._FormApprovedOMBNo.2070.0060UNITEDSTATESENVIRONMENTALPROTECTIONAGENCYI"""'''''401MStreet,S.W.WASHINGTON,D.C.20460PaperworkReductionActNotice:Thepublicreportingburdenforthiscollectionofinformationisestimatedtoaverage0.25hoursperresponseforregistrationactivitiesand0.25hoursperresponseforreregistrationandspecialreviewactivities,includingtimeforreadingtheinstructionandcompletingthenecessaryforms.Send commentsregardingtheburdenestimateoranyotheraspectofthiscollectionof'lnformation,includingsuggestionsforreducingtheburdentoDirector.OPPEInformationManagementDivision(2137)U.S.EnvironmentalProtectionAgency,401MStreet,S.W.,Washington,DC20460.Donotsendtheformtothisaddress.DATAMATRIXDate:September10,2009EPARegNo.lFileSymbol2517-NEWPage1of2Applicant's/Registrant'sName&AddressProduct:EtofenproxlNylarSpot-OnFleaandSergeant'sPetCareProducts,Inc.2637South158thPlaza,Suite100,Omaha,NE68130-1703TickforDogsandPuppiesIngredients:EtofenproxandPyriproxyfenGuidelineReferenceNumberGuidelineStudyNameMRIDNumberSubmitterStatusNote830.1550,1600,1620,1650,ProductPropertiesData46161301Sergeant'sPetCareProducts,Inc.OWN1670,1750,1800830.6302,830.6303,830.6304,Productchemistry46161302Sergeant'sPetCareProducts,Inc.OWN830.7300,830.7000,830.6315,830.7100,830.6320,830.6317830.6317,830.6320Storagestabilityandcorrosioncharacteristics46700801870.1100Acuteoraltoxicity46161303Sergeant'sPetCareProducts,Inc.OWN870.1200Acutedermaltoxicity46161304Sergeant'sPetCareProducts,Inc.OWN870.1400Primaryeyeirritation46161305Sergeant'sPetCareProducts,Inc.OWN870.1500Primarydermalirritation46161306Sergeant'sPetCareProducts,Inc.OWN870.1600Dermalsensitization46161307PetCareProducts,Inc.OWN870.7200CompanionAnimalSafetyEvaluationonDogsNewsubmissionSergeant'sPetCareProducts,Inc.OWN810.3300Efficacyofawater-basedetofenproxspot-onagainstNewsubmissionSergeant'sPetCareProducts,Inc.OWNfleasandticksonsmalldogsResidentialexposureandriskassessmentforaNewsubmissionSergeant'sPetCareProducts,Inc.OWNproposedetofenproxspot-onproductfordogsSignature:"n.NameandTitleRJ;,eLJamesMessina,AuthorizedRepresentative'-"n<10.<".,n0<,n"'''e,•••••D.__•,,__,.__....:1."'_",..__,..n'_QO"Q••'__Tn#A___'n<Ar__,"-'}..FormApproyedOMBNo.2070·0060UNITEDSTATESENVIRONMENTALPROTECTIONAGENCY"401MStreet,S.W."WASHINGTON,D.C.20460PaperworkReductionActNotice:Thepublicreportingburdenforthiscollectionofinformationisestimatedtoaverage0.25hoursperresponseforregistrationactivitiesand025hoursperresponseforreregistrationandspecialreviewactivities,includingtimeforreadingtheinDeregistrationcompletingthenecessaryforms.Sendcommentsregardingtheburdenestimateoranyotheraspectofthiscollectionofinformation,includingsuggestionsforreducingtheburdentoDirector:OPPEInformationManagementDivision(2137)U.S.EnvironmentalProtectionAgency,401MStreet,S.W.,Washington,DC20460.Donotsendtheformtothisaddress.DATAMATRlXDate:September10,2009EPARegNo.lFileSymbol2517-NEWPage2of2Applicant'slRegistrant'sName&AddressProduct:EtofenproxlNylarSpot-OnFleaandSergeant'sPetCareProducts,Inc.2637South158'"Plaza,Suite100,Omaha,NE68130-1703TickforDogsandPuppiesIngredients:EtofenproxandPyriproxyfenGuidelineReferenceNumberGuidelineStudyNameMRiDNumberSubmitterStatusNote810.3300EfficacyataminimumdoserateofanetofenproxNewsubmissionSergeant'sPetCareProducts,Inc.OWNspot-onagainstfleasandticksonsmalldogs810.3300Efficacyatlabel dosevolumeandatminimumdoseNewsubmissionSergeant'sPetCareProducts,Inc.OWNrateofanetofenproxspot-onagainstfleasandticksonsmalldogs810.3300EvaluationofSergeant'setofenproxsqueeze-onNewsubmissionSergeant'sPetCareProducts,Inc.OWNagainstfleas,ticksandmosquitoesondogs810.3300EfficacyofSergeant'setofenproxsqueeze-onagainstNewsubmissionSergeant'sPetCareProducts,Inc.OWNIxodesscapularisnymphs810.3300Efficacyofa2mLunitdoseofSergeant'setofenproxNewsubmissionSergeant'sPetCareProducts,Inc.OWNsqueeze-onappliedatminimumdoserates,againstfleasandticksonsmalldogs810.3300DataanalysisofadosetitrationtodeterminetheNewsubmissionSergeant'sPetCareProducts,Inc.OWNrelationshipbetweendoserateofetofenproxwhenappliedasaspot-ontodogsandthedurationofresidualefficacyagainstfleasandtickreinfestation810.3300AnalysesofefficacyandsafetydatatosupportlabelNewsubmissionSergeant'sPetCareProducts,Inc.OWNclaimsforSergeant'ssqueeze-onforsmalldogscontainingetofenproxandpyriproxyfen/Signature:\VL,.NameandTitleJamesMessina,AuthorizedRepresentative-.-......-....,Fo=No.2070-0060UNITEDSTATESENVIRONMENTALPROTECTIONAGENCY401MStreet,S.W.WCTT".rrVIV,."TD.C.20460PaperworkReductionActNotice:Thepublicreportingburdenforthiscollectionofinformationisestimatedtoaverage0.25hoursperresponseforregistrationactivitiesand0.25hoursperresponseforreregistrationandspecialreviewactivities,includingtimeforrcadingtheinstructionandcompletingthenecessaryfonus.Sendcommentsregardingtheburdenestimateoranyotheraspectofthiscollectionofinformation,includingsuggestionsforreducingtheburdentoDirector:OPPEInformationManagementDivision(2l37)U.S.EnvironmentalProtectionAgency,401MStreet,S.W.,DC20460.Donotsendthefonntothisaddress.Sergeant'sPetCareProducts,Inc.Sergeant'sPetCareProducts,Inc.OWNSergeant'sPetCareProducts,Inc.OWNforreregistrationandcollectionofinformaUNITEDSTATESENVIRONMENTALPROTECTIONAGENCY'"401MStreet,S.W.'"WD.C.toaverage0.25hoursperresponseforregistrationactivitiesand0.25hoursperresponseactivities,includingtimeforreadingtheinOeregistrationcompletingthenecessaryforms.SendcommentsregardingtheburdenestimateoranyotheraspectofthisforreducingtheburdentoDirector:OPPEInformationManagementDivision(2137)U.S.EnvironmentalProtectionAgency,401MStreet,S.W.,Inc.Inc.Sergeant'sPetCareProducts,Inc.Sergeant'sPetCareProducts,Inc.Inc.AuthorizedInternalUseCopy

# Sergeant's 

# _et**~are** 

# Products, Inc.**~tla~ter** 

# Label
10 September 2009 EPA Reg. No. 2517-XX Information in [ ] is optional. Page I of4 EPA SAL 

## FRON'I'..J'A$r,·/··

..;. ...•..••.•.....•..•..**...........~()(;SQPl!:E2;~;;;-0N**

### :Ryripr(Jiifeil&¥tlR),!ttQ(en~~o~ Editors Note: [Optional proposed text appears in brackets

- the final label may include some or all ofthe optional text]
ETOFENPROXJNYLAR SPOT-ON FLEA AND TICK FOR DOGS AND PUPPIES
{ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On} {ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small breed dogs} {ABN: Sergeant's Toy Breed Flea and Tick Squeeze-On for small and toy breed dogs} {ABN: Sergeant's Small Breed Flea and Tick Squeeze-On} {ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small breed dogs} {ABN: Sergeant's Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for dogs} {ABN: SentryPro Toy and Small Breed Flea and Tick Squeeze-On for small and toy breed dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for Dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small breed dogs} {ABN: SentryPro Small Breed Flea and Tick Squeeze-On for small and toy breed dogs}
[One Application:(choose from the following)]

• [with nylar®]

• [(One) (Two) (Three) (Four) (XX) Applications]

• [Bonus] 33% more [now includes 4 tubes]

• [odorless] [unscented] [ fragrance free]

• [Quick Acting] [&] [Long Lasting]

• [Dries quickly] [Quick drying formula] [Quick Drying]

• [Squeeze-On] [stays on and doesn't rub off]

• [Spreads by using the dog's natural skin oils]

• [Breaks the flea life cycle for up to (70 Days) (9 Weeks)]

• [Controls reinfestation for up to (70 days) (9 weeks)]

• [For toy breeds 4-20 Ibs.]

• [For small breeds 4-20 Ibs.]

• [For toy and small breeds 4-20 Ibs.]

• [Specially formulated for small breed[s] dogs]

• [Specially formulated for toy breed[s] [dogs]]

• [Specially formulated for [toy breed[s]] and [small breed[s]] dogs]

• [Toy] [and] [small] breed formula]

• [Gentle protection for [toy] [small] breed dogs]

• [5 Way Protection]

• [Controls fleas, ticks, mosquitoes, flea eggs & larvae]

• [Kills Fleas, Ticks, Flea Eggs, Larvae] [and repels mosquitoes]

• [Flea, tick, mosquito, flea egg and larvae control]

• [Kills ticks]

• [Kills Ticks] [Before they can] [that] [transmit Lyme Disease]

• [Kills adult fleas]

• [Kills Fleas and Ticks]

• [Flea, Tick and Flea Egg Protection]

• [Flea, Tick and Mosquito control]

• [Kills fleas that may cause flea allergy dermatitis, and flea bite anemia]

• [Kills Flea Eggs and Larvae for up to (9 weeks) (70 days) (per application)] 

# . , ,

;}} )

..

J; , "') )

, ) } }

)'; ,

,,) 2

• [prevents flea eggs from developing into biting adults for up to (9 weeks) (70 days) (per application)]

• [Repels mosquitoes that may transmit [heartworm] [West Nile virus] [from feeding on dogs]

• [Repels Mosquitoes] [Prevents mosquitoes that transmit West Nile virus and heartworm] [from feeding on dogs]

# Sergeant's -"- 

# h (:are Products,**Inc.J1Cl~ter** 

# Label
10 September 2009 EPA Reg. No. 2517-XX Information in [ ] is optionaL Page 2 of4 EPA SAL

ACTIVE INGREDIENTS: Etofenprox

...................................................................................... 55.00% Pyriproxyfen..

.... ........... ......... ..... ..... ... ...... .......... ............ ...... .......... 2.20% OTHER INGREDIENTS:

........................................................................ 42.80% TOTAL 100.00%
[Nylar® is a registered trademark ofMcLaughlin Gonnley King Company]



### KEEP OUT OF REACH OF CHILDREN 

### CAUTION See [Back][or][Side] Label Panel[s] for Additional Precantionary Statements

NET CONTENTS: [One] [Two][Three][Four][Five][Six] 2.0 mL applicators. 

### {for small dogs 4 

### to 20 IbsJ



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# Label
10 September 2009 EPA Reg. No. 2517-XX Information in [ ) is optional. Page 3 of4 EPA SAL

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READ ENTIRE LABEL BEFORE EACH USE

PRECAUTIONARY STATEMENTS HAZARDS TO HUMANS AND DOMESTIC ANIMALS 

### CAUTION

HAZARDS TO HUMANS: Causes moderate eye irritation. Avoid contact with eyes and clothing. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, or using tobacco.

HAZARDS TO DOMESTIC ANIMALS: For External Use Only. Do not use on dogs under 12 weeks of age. Consult a veterinarian before using this product on debilitated, aged) medicated, pregnant, or nursing animals. Sensitivities may occur after using ANY pesticide product for pets. Ifsigns of sensitivity occur, bathe your pet with mild soap and rinse with large amounts afwater. Ifsigns continue, consult a veterinarian immediately.

FIRST AID
IF IN EYES: Hold eye open and rinse slowly and gently with water for 15-20 minutes. Remove contact lenses, if present, after the first 5 minutes, and then continue rinsing. Call a poison control center or doctor for treatment advice. Have the product container or label with you when calling a poison control center or doctor or going for treatment. You may also contact 1-800-781-4738 for emergency medical treatment information.

PHYSICAL OR CHEMICAL HAZARDS: Combustible: Do not use or store near heat or open flame.

DIRECTIONS FOR USE It is a violation of Federal Law to use this product in a manner inconsistent with its labeling.

Do not get this product in your pet's eyes or mouth. Do not apply more often than [once a month] [once every 30 days]. Use only on Dogs. FOR EXTERNAL USE ON DOGS ONLY. Do not use on puppies less than 12 weeks ofage. Weigh your dog to be sure you are applying the right dose formulated for the weight ofyour pet. Do not treat your pet with more than one pesticide product at a time. Over dosing your animal can result in serious illness and even death. Best ifused year round. Do not bathe pet with in the first 24 hours after squeeze-on has been applied. Households with more than one pet should not allow dogs or cats to groom each other until solution has, dried. DO NOT USE ON CATS or animals other than dogs. Separate the treated dog from all other dogs and**c~ts** for 24 hours after treatment has been applied. Cats or dogs that actively groom or engage in close physical**c~nt~ep** , with treated dogs may be at risk ofserious harmful effects. Ifyour dog is exhibiting signs ofanrlJopofO**being1re&(~d** for skin dermatitis, talk to your vet before applying any topical flea and tick control product. sopsidviiies may oc'cur after using ANY pesticide product on pets. It is recommended to separate treated dogs from othrl P9viehold PPI")"'; 24 hours after treatment has been applied. If signs of sensitivity occur, bathe your dog with mild**~oap~and** rinse with large amounts ofwater. ' ) } ) t , ) } , ) , " } , 1 FOR USE ON DOGS: $ t } % Weighing 4 TO 20 LBS.

- Apply contents ofone (2.0 mL) tube [vial] of [Product Name) [Squeeze-on) as a'sp.?! , ' high on the back ofthe dog's neck behind its head and apply as a stripe to a point midway between the neck "I'd 

### tfit tail. ),;)} (INSERT DIAGRAM THAT DEPICTS APPLICATION OF PRODUCT ON THE DOG)

HOW TO APPLY: Remove product tube [vial] from the package. Holding tube [vial] with notched end pointing up and away from the face and body cut or tear offthe narrow end at the notches. While holding the animal with one hand, use the other hand to apply the solution. Invert the tube [vial] and use the narrow end to part the animal's hair while gently squeezing to apply to the animal's skin. Hold the animal for a few seconds to give the solution time to be absorbed into the animal's coat. When finished, wrap the tube [vial] in paper and put into the trash.

# Sergeant's

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# h tare Products, Inc.**~naster** 

# Label

10 September 2009 EPA Reg. No. 2517-XX Information in [ ] is optional. Page 4 of4 EPA SAL

STORAGE AND DISPOSAL Do not contaminate water, food or feed by storage or disposal. PESTICIDE STORAGE: Do not remove tube from the pack until ready to use. Store in a cool (below 25°C) dry place out ofreach ofchildren. Do not refrigerate. Protect from direct sunlight.

PESTICIDE DISPOSAL: Nonrefillable container. Do not reuse or refill this container. Offer for recycling or reconditioning, if available and appropriate. If empty: Do not reuse this container. Place in trash or offer for recycling ifavailable. Ifpartly filled: Call your local solid waste agency for disposal instructions. Never place unused product down any indoor or outdoor drain.

[WARRANTY Read the entire Directions for Use and Warranty before using this Product. By using this product, user or buyer accepts the following warranty. [[The directions for use ofthis product are believed to be adequate and must be followed carefully. However, it is impossible to eliminate all risks inherently associated with the use ofthis product. Unintended consequences may result because of such factors as weather conditions, presence or absence ofother materials, or the manner ofapplication, all ofwhich are beyond the control ofSergeant's Pet Care Products, Inc

..]] Sergeant's Pet Care Products, Inc. is committed to providing high quality products. To the extent consistent with applicable law, Sergeant's Pet Care Products, Inc. makes no warranties, express or implied, ofmerchantability or of fitness for a particular purpose or otherwise, that extend beyond statements on this label. To the extent consistent with applicable law, Sergeant's Pet Care Products, Inc., the manufacturer, or the Seller disclaims any liability whatsoever for special, incidental, or consequential damages reSUlting from the use ofthis product. To the extent consistent with the law, the exclusive remedy ofthe user or buyer shall not exceed the purchase price paid.]
[Sergeant's Care Pet Products, Inc. is committed to providing high quality products. Ifyou have questions or comments about this product,.please write: Sergeant's Consumer Response, P.O. Box 540399, Omaha, NE 68154- 0399.]

In Case ofEmergency, call: 1-800-781-4738 Non-Emergency call: 1-800·224-PETS (7387)

Distributed by:
Sergeant's Pet Care Products, Inc. PO Box 540224 Omaha, NE 68154 {END

- BACK / SIDE PANEL)

### [Q.EfFr?M~g:~~~~1 Front Label {Product Name) Etofenprox

..........55.0% W/W Pyriproxyfen

........ .2.2% W/W 2.0mL {label code) [For more information] [Visit us at:] www.sergeants.com Made in USA

EPA Reg. No. 2517-XX EPA Est. No. XXXXXXX {date & label code)

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### Back Label " "

KEEP OUT OF REACH OF Chll/,);)REN "" CAUTION: Read directions and predutions**bef~re** )**~** ; ] ) using. 

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